Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
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cyclin dependent kinase inhibitor 1A(CDKN1A) cyclin dependent kinase inhibitor 1A(CDKN1A) Related Genes Homo sapiens
CHROMOSOME 6,
CYTOBAND 6p21.2,
ENSEMBL_GENE_ID ENSG00000124762,
ENTREZ_GENE_ID 1026,
GENERIF_SUMMARY expression is related to apoptosis in thymus, p21CIP1/WAF1 was able to repress the immortal phenotype. CDKIs mediate growth arrest in human osteosarcoma cell lines and provides further evidence of the existence of molecular links between cellular mortality and immortality., tested for inhibition of Plasmodium falciparum cyclin dependent protein kinases, In the ovarian cancer cell lines studied, cell growth was inhibited after transfection with p16(INK4a), p21(WAF1/Cip-1), and p53., Cdk4 activity does correlate with changes in the level of the Cdk inhibitor p21(WAF1/Cip1, induced after DNA damage and plays a role in cell survival, Overexpression of p21(WAF1/CIP1) is an early event in the development of pancreatic intraepithelial neoplasia., The ability of p21(Cip1) to inhibit cyclin D1 nuclear export correlates with its ability to bind to Thr-286-phosphorylated cyclin D1 and thereby prevents cyclin D1.CRM1 association, phosphorylation by AKT/PKB enhances protein stability and promotes cell survival, expression inhibited by Hepatitis C virus core protein, expression in normal, hyperplastic and carcinomatous human prostate, Loss of the p21(Cip1/Waf1) cyclin kinase inhibitor results in propagation of horizontally transferred DNA., hinge region of the human papillomavirus type 8 E2 protein activates the human p21(WAF1/CIP1) promoter via interaction with Sp1, The expression of p21(WAF1/CIP1) was higher in the skin of arsenic intoxication than in controls., We investigated three common sequence variants in TP53 and p21 for possible associations with the risk of breast cancer and with various phenotypic features of this disease, Inhibition of bone marrow stem cell proliferation by retinol was mediated by the up-regulation of cyclin-dependent kinase inhibitors, p21(Cip1) and p27(Kip1)., The onset of ATRA-induced G(0)/G(1) arrest of U-937 cells is linked to an increase in p21(WAF1/CIP1) expression., Role of p21 in apoptosis and senescence of human colon cancer cells treated with camptothecin, Specific inhibition of p21(Waf1/Cip1) protein with the antisense oligodeoxynucleotide markedly reduces the production and secretion of the matrix proteins fibronectin and laminin, both in the presence and absence of TGF-beta stimulation., Early induction of CDKN1A (p21) and GADD45 mRNA by a low dose of ionizing radiation is due to their dose-dependent post-transcriptional regulation, REVIEW, Expression of p21WAF1 is dependent on the activation of ERK during vitamin E-succinate-induced monocytic differentiation., Negative regulation of cell growth and differentiation by TSG101 through association with p21(Cip1/WAF1)., cyclooxygenase-2 inhibitor induces G0/G1 cell cycle arrest in NA cells by upregulation of p21, expression in pelvic lymph nodes and primary tumors in early stage cervical carcinomas, Correlation of p21 gene codon 31 polymorphism and TNF-alpha gene polymorphism with nasopharyngeal carcinoma., Results suggest that p21(Cip/WAF1) and cyclin D1 induction may result from the activation of the ERK and PI-3 kinase pathways., A strong inhibition of cell proliferation was observed in K562-p21(WAF1) cell as compared with that of the control, and the cell number in G(0)/G(1) phase was remarkably increased., interferon-alpha exerts antitumor effects by increased p21 expression in neuroendocrine tumors, Review of the influence of histone acetylation and DNA methylation on p21(WAF1) transcription, and affection of pathways or factors associated such as p 53, E2A, Sp1 as well as several histone deacetylation inhibitors., Cell attachment to the extracellular matrix induces proteasomal degradation of p21(CIP1) via Cdc42/Rac1 signaling (P21CIP1), H(2)O(2)-induced AP-1 activation and its effect on p21(WAF1/CIP1)-mediated G2/M arrest in a p53-deficient human lung cancer cell., Identification of the regulatory region required for ubiquitination of the cyclin kinase inhibitor, p21., Oxidized low density lipoprotein induces the cyclin-dependent kinase inhibitor p21(waf1) and the tumor suppressor Rb., results suggested that p21 is up-regulated by the stress of inflammation and fibrosis in hepatitis C virus (HCV)-associated chronic liver diseases and that high p21 expression might be related to hepatocarcinogenesis in cirrhotic patients, stabilization by phosphorylation influenzed by protein kinase p38 alpha and JNK1, p21/WAF1 expression associated with endocrine activity in pituitary adenomas; tumors expressing cytoplasmic p21/WAF1 may have resistance to DNA-damaging agents such as ionizing radiation, P27Kip1 immunoreactivity is higher in male breast cancers compared with female breast cancers., transcriptional regulation of p21 CIP1 WAF1 controls p53 independent ovarian cancer apoptosis, C/EBPalpha is essential for p21-mediated inhibition of G1 to S-phase progression by RAP in KSHV-infected host cells, role in modulating threshold of apoptosis induced by DNA-damage and growth factor withdrawal in prostate cancer cells, Sp1-mediated activation of p21(WAF1/CIP1) expression is accompanied by G(1) cell cycle arrest induced by 3,3'-diindolylmethane in human breast cancer cells, inactivation sensitizes cells to apoptosis via an increase of both p14ARF and p53 levels and an alteration of the Bax/Bcl-2 ratio, Mutations of the cell cycle arrest gene p21WAF1, but not the metastasis-inducing gene S100A4, are frequent in oral squamous cell carcinomas from Sudanese toombak dippers and non-snuff-dippers from the Sudan, Scandinavia, USA and UK., p21(CIP1/WAF1) protein expression was increased in AMs and biopsies isolated from smokers and was found predominantly within the cytoplasm., Msx2 and p21(CIP1/WAF1) mediate the proapoptotic effects of bone morphogenetic protein-4 on ventricular zone progenitor cells., Cleavage of p21waf1 by proteinase-3, a myeloid-specific serine protease, potentiates cell proliferation, relationship of Mcl-1 isoforms, ratio to cyclin A and Jun kinase phosphorylation to apoptosis in human breast carcinomas, p21(cip1) induction is interrupted by ROCK-mediated signal transduction in preapoptotic cells, The proximal p21(WAF-1/Cip1) promoter region has been characterized and the contribution of individual Sp1 binding sites to both constitutive and inducible promoter activity in hepatocytes is analyzed in detail., By inhibiting p21(Cip1) expression Myc favours the initiation of apoptosis, thereby influencing the outcome of a p53 response in favour of cell death, role of PIN1 in transactivation, insulin inhibits TNF-alpha-dependent cell killing, induction of p53, p21 and apoptosis in a human cervical carcinoma cell line, Forced expression of STAT5a in human cord blood-derived CD34+ cells enhanced expression Bcl-2 and p21(WAF/Cip1), suggesting they may be important in STAT5a-mediated eosinophil differentiation., Oxidative stress induces rapid, but reversible, downregulation of functional p21 by accelerating its protein turnover., In conclusion, no polymorphism exists in codon 149 of P21(Waf1/Cip1)., Lack of p21(CIP1) DNA methylation was found in 31 patients with acute lymphocytic leukemia., promoter elements responsible for transcriptional inhibition of polo-like kinase 1 and topoisomerase IIalpha genes by p21(WAF1/CIP1/SDI1), The 3'-untranslated region of this protein's mRNA is a composite cis-acting sequence bound by RNA-binding proteins from breast cancer cells, including HuR and poly(C)-binding protein., cyclin kinase inhibitors p21 are associated with laryngeal papillomas., LMP1 inhibits transforming growth factor-beta 1-mediated induction of MAPK/p21 in Epstein-barr virus infected gastric epithelial cell line GT38, Hepatitis C virus NS4A and NS4B proteins at inhibited p21/Waf1 expression post-transcriptionally, p21(waf1) has a role in aortal endothelial cell aging, Codon 31 polymorphism is associated with bladder cancer, WAF1 degradation is regulated by atypical PKC and PDK1, p21(WAF1) transfection decreases sensitivity of K562 cells to VP-16, A direct role is demonstrated for p21 in suppressing spontaneous IL-6 and MMP-1 production in rheumatoid arthritis synovial fibroblasts, whereas p21 overexpression has no effect on IL-6 or MMP-1 production in normal and osteoarthritic synovium., p21 expression is regulated via a mechanism that is suppressed by PP5, p21 expression correlates positively with proliferation in oral squamous cell carcinoma. Up-regulation of p21 is associated with early progression., Downregulation of waf1 mediates apoptosis of human hepatocellular carcinoma cells in response to interferon-gamma., repression of p21 promoter/reporters as well as the endogenous p21 gene by Myc depends on interaction with Miz-1. Expression of Miz-1 increases during hematopoietic differentiation and Miz-1 activates the p21 promoter under conditions of low Myc levels, CDK2 activity was reduced dose-dependently after 24 h of ZD1839 treatment and this effect correlated with increased amount of p27(KIP1) and p21(CIP1/WAF1) associated with CDK2-cyclin-E and CDK2-cyclin-A complexes in head/neck squamous carcinoma cell lines, TNFalpha mediates cellular growth arrest through activation of the transcription factor NF-kappaB. The cdk inhibitor p21(Cip1/Waf1) is activated through NF-kappaB and is an important mediator of this growth arrest response, activation by insulin-like growth factor 1 inhibits UV-induced cell death, Gene expression is increased in chronic allograft nephropathy and coorelates with the number of acute rejection episodes., Upon prolonged exposure, progestins activate p53, in human breast and endometrial tumor cells, which up-regulates the p21(Cip1,Waf1) promoter., deacetylase HDAC1 acts as an antagonist of the tumor suppressor p53 in the regulation of the cyclin-dependent kinase inhibitor p21, Abolition of p21(Cip1/Waf1) and p16(Ink4a) functions prevented oncogenically activated Ras from inducing growth arrest and was sufficient for limited anchorage-independent growth but not tumorigenesis., The growth inhibitory action of ATR is associated with the activation of p21WAF1., These results suggest that the delay of senescence in cultures grown in the presence of dexamethasone is due to a suppression of the senescence related increase in p21(Waf1/Cip1/Sdi1)., Egr1 controls p21Cip1 expression by directly interacting with a specific sequence on its gene promoter., Inhibitor shows antitumor effect on glioma cells., Investigations confirmed the rarity of mutations in this gene, arguing against a role for TP21 mutations in skin, head, and neck cancers., p21waf1/cip1 is down-regulated in the lymphocytes of rheumatoid arthritis patients., Mutant p53 can delay growth arrest in senescing fibroblasts without reducing p21(WAF1) expression., laminar flow caused an increase of p21Waf1 level in the wild-type HCT116 (p53+/+) cells but not in the p53-null HCT116 cells, Data show that tetradecanoylphorbol acetate activated p21(WAF-1) expression by a protein kinase c-dependent mechanism and that one specific Sp1 binding site in the p21(WAF-1) promoter was critically essential for this activation., CDKN1A and CDKN1B variants are associated with advanced prostate cancer., expression of p21/CDKN1A is necessary and sufficient for the negative regulation of gene expression by p53, Reduced expression of p21 and p27, being VDR dependent, is major pathogenic factor for nodular parathyroid gland growth in advanced secondary hyperparathyroidism. Review., Presence of p53 Pro allele and/or p21 Arg allele is associated with lower downstream target gene expression of p21, Histone deacetylase inhibitors activate p21(WAF1) expression via ATM., In carcinoma in situ without muscle-invasive disease, positive p21 expression is independently associated with bladder cancer recurrence and progression., The TGF-beta-1-induced decrease in CDK2 kinase activity was the result of increased p21 association with cyclin A-CDK2 and cyclin E-CDK2. , p21 induction in early G(1) is critical for TGF-beta 1 inhibition of CDK2 kinase activity., ErbB positive status was associated with p21 overexpression in human ductal carcinoma in situ., The dysfunction of p21 in NB cells represents a novel mechanism by which the G(0)-G(1) cell cycle checkpoint can be inactivated., p21 is highly correlated with p73 expression irrespective of the p53 mutation status in human esophageal cancers, p21WAF1 binding to HDAC1 is disrupted by Che-1 protein in human colonic carcinoma, p53RFP, a p53-inducible RING-finger protein, regulates the stability of p21WAF1., p21(WAF1) has a role in drug-induced senescence in colorectal cancer cells, p21CIP/WAF is a positive regulator in the cell proliferation induced by IGF-I in MCF-7 cells., The differences in apoptotic activity and p21(WAF1/CIP1) expression between serrated adenomas (SA) and traditional adenomas or hyperplastic polyps indicate that SA should be considered as a distinct subtype of colorectal neoplasm, High expression of p21 Waf1 is associated with sarcoid granulomas, Hepatitis C virus (HCV) core protein potentially modulates hepatocyte cell cycle differentially in the early stages of infection through biphasic regulation of p21 cdk kinase inhibitor, p21 is required for the G1/S arrest of HCT116 colon cancer cells but its mode of action is more complicated than the simple formation of a physical complex with cyclin-Cdk2, PARP-1 and p21 could cooperate in regulating the functions of PCNA during DNA replication/repair., p21 has an antiapoptotic role in monocytic leukemia., exposure in vitro to hyperoxia exerts G(1) arrest through p53-dependent induction of p21 that suppresses Cdk and PCNA activity., p21WAF1/CIP1, pRB, Bax and NF-kappaB have roles in induction of growth arrest and apoptosis by resveratrol in tumor cell lines, p21 is a transcriptional target of CDX2. Our results may thus provide a new mechanism underlying the functions of CDX2., UV-induced p21 degradation is essential for optimal DNA repair, These results suggest that in vivo p21CDKN1A does not interfere with loading of PCNA at DNA replication sites, but prevents, or displaces subsequent binding of DNA polymerase delta to PCNA at the G1/S phase transition., the association of p21 and cyclin A in response to gamma-irradiation requires the CDK2 binding region, Cytoplasmic p21WAFI/CIPI may be a surrogate marker of functional HER-2 in vivo., Resveratrol caused a dose-dependent increase in intracellular p53 and p21(WAF1/CIP1) levels., p21 down-regulation is multiply determined and is required for the reversibility of the arrest in S phase, Codon 31 polymorphism in p21 may be associated with the development of esophageal cancer, Low p21 protein level is associated with advanced TNM stage and positive nodal status of squamous cell carcinoma of hypopharyngeal cancer, In adenocarcinomas, no statistically significant correlation was found between K-ras mutational status and p21WAF1/CIP1 and p53 expression., MDM2 directly inhibits p21waf1/cip1 function by reducing p21waf1/cip1 stability in a ubiquitin-independent fashion, We conclude, therefore, that two major components of cell-cell interaction synergistically regulate cell cycle progression in HEK293 cells by regulating p21 expression in a beta-catenin/TCF-dependent manner., in hepatocellular carcinoma, PCNA participates both in DNA synthesis and repair and that highly proliferating cancers may display a sustained DNA-repair., how HO-1 and WAF1/Cip1 were regulated in two gastric cancer cell lines, cyclin-dependent kinase inhibitor 1A (p21) levels rise abruptly in individual aging cells and remain elevated for extended periods of time., Promoter is hypermethylated in various lymphomas and carcinomas., NaB-induced apoptosis required P21(waf1/cip1) and its interaction with PCNA., We present evidence that p21(WAF1) is required for 9-HSA mediated growth arrest in human colon carcinoma cells, Assessment of p21, p27, Bax, and cyclin E expression in tumor tissues have been reported to be useful as prognostic factors in head and neck squamous cell carcinoma., Perifosine increases Sp1 binding and enhanced p21(waf1/cip1) transcription., Abnormally high amounts of Stat1, Stat5 and p21Cip1 proteins were found in prehypertrophic-hypertrophic chondrocytes, the extent of overexpression being directly related to the severity of the disease, Overexpression of integrin beta1 imposed a growth inhibitory effect on a liver neoplastic cell line which is mainly attributed to CIP1., by reducing p21 protein stability via proteasome-mediated degradation, MDM2 functions as a negative regulator of p21, TGF-beta-Smad signaling pathway inhibits the growth of human epithelial cells and plays a role in tumor development., Loss of p21 and/or p53 might not predict for prognosis in oropharnyggeal squamous cell carcinoma., Transactivation of the CIP1 promotor by fetal liver kinase-3 mutations involves stat5 binding site., Flavopiridol abrogates depsipeptide mediated induction of p21 expression via inhibition of protein kinase C signaling in malignant pleural mesothelioma cells., simultaneous expression of HPV-16 E7 protein and p21 proteins induces apoptosis and activates cathepsin B, Results suggest that basic helix-loop-helix proteins provide a direct transcriptional link between a cell cycle inhibitor, p21(Cip1), and a neurotrophic receptor, Trk., p21WAF1 in vascular smooth muscle cells is regulated by transcription factor Sp1 and p38MAPK, In human colon cancer cell lines, HDAC inhibitors stimulate the p21(WAF1) gene expression by selectively increasing the degree of acetylation of the gene-associated histones., The expression patterns of cyclin D1, cyclin E, p21/waf1 and p27/kip1 in inflammatory bowel disease (IBD) may indicate their contribution in epithelial cell turnover and their possible implication in IBD-related dysplasia-carcinoma., The expression of p21 protein depends on p53 protein largely in normal gastric mucosa and dysplasia, but not in gastric carcinoma., role of pathway in regulating G1-S transition and apoptosis along with RFT, Results suggest that p150(Sal2), acting in part as a p53-independent regulator of p21 and BAX, can function in some cell types as a regulator of cell growth and survival., p21(Waf1) can activate the transcription of p16(INK4); this effect is GC-box dependent; and the transcription factor Sp1 plays a key role in this event, hepatitis B virus X protein natural variants have differential effects on p21 expression, activation of the p53-p21WAF1 pathway and overexpression of cyclin D1 are induced during tumor cell differentiation by beta-catenin, Low p21 protein levels are caused by reduced p21 gene transcription and sensitize cisplatin-treated TGCT cells to the Fas death pathway, p21 or p21B do not have a role in causing resistance to doxorubicin or mitomycin/5-fluorouracil in breast cancer, p21/waf1 could potentially function as an assembly factor in HTLV-1 infected cells., Data suggest that dihydrotestosterone reverses titration of p21(Cip1/Waf1) and p27(Kip1) away from Cdk2 complexes, and increased association of p21 with Cdk2 complexes mediates the androgen-induced growth inhibition of breast cancer cells., p21Cip1/WAF1 and HER2/neu togehter have a role in progression of breast neoplasms, in normal cells, p21 exerts a dual role in mediating DNA damage-induced cell cycle arrest and exit before mitosis, Data show that ERK1/2-mediated phosphorylation of hepatitis B viral X-gene (HBx) regulates HBx function and localization, and that HBx repressed transcription from the p21(WAF1/Cip1) promoter., hRAD9 and p53 co-regulate p21 to direct cell cycle progression by similar molecular mechanisms., P21 expression stimulates promoters of six p21-responsive human genes and the cytomegalovirus promoter, as well as an artificial promoter containing NFkappaB response elements., Disruption of p53-p21/WAF1 cell cycle pathways contributes to tumor progression and worse clinical outcome of hepataocellular hepatoma., Relation between expression, DNA ploidy and human papillomavirus infection in cervical carcinoma., Data show that extracellular signal-regulated kinase 3 (ERK3) is conjugated to ubiquitin via its free NH(2) terminus, and that N-terminal tags stabilize expression of p21 but not that of substrates ubiquitinated on internal lysine residues., p53 and/or p21(WAF1/CIP1) genotype may influence the progression during gastric tumorigenesis., p21WAF1 gene expression is regulated by histone deacetylase inhibitors at the post-transcriptional level in HepG2 cells, Stat3 mediates expression of p21waf1., Cyclin D1, p53, and p21Waf1/Cip1 have roles in progression of serous epithelial ovarian cancer, physical interaction of Vpr with Sp1 and p53 could modulate transcriptional activity of p21., Histone acetylation regulates p21WAF1 expression in human colon cancer cell lines, Colo-320 and SW1116., pdcd4 represses the transcription of the mitosis-promoting factor cyclin-dependent kinase (CDK)1/cdc2 via upregulation of p21(Waf1/Cip1), Monocytic differentiation of the promyelomonocytic cell lines U937 and HL60 is associated with the upregulation of Brap2 expression concomitantly with the upregulation and cytoplasmic relocalization of p21., P21Cip1 positively regulates the cytotoxic action of thymidylate synthase inhibitors, negatively regulates the cytotoxic action of IFN-gamma, and enhances S-phase exit after thymineless stress in colorectal carcinoma cells., Cystathionine gamma-lyase has a role in regulating cell proliferation via a H2S-dependent modulation of ERK1/2 phosphorylation and p21Cip/WAK-1, Tax1 markedly activated transcription from the cdk inhibitor p21(cip1/waf1) promoter in comparison to Tax2, suggesting that upregulation of p21(cip1/waf1) may account for the differential inhibition of cellular replication kinetics, repression of hTERT by endogenous p53 is mediated by p21 and E2F, PGA2 stabilizes the p21 mRNA through an ERK-independent increase in cytoplasmic HuR levels and an ERK-dependent association of HuR with the p21 mRNA, absence of p21 produced no overt alteration of the lifespan of the INK4a/ARF-null mice, We conclude that overexpression of PKCdelta in human colon cancer cells induces multiple antineoplastic effects that depend on the activities of p21(Waf1/Cip1) and p53., p21(WAF1), acting through the phosphorylation of pRb, regulates whether 2BS cells cease to proliferate and become senescent but resistant to apoptosis, or whether they accelerate proliferation while becoming more susceptible to apoptotic stimuli, survivin can reduce the cell growth inhibition and apoptosis, and p53 elevates the p21 level, which may attenuate the cell death in the quercetin-treated human lung carcinoma cells, c-myc downregulation and release from the endogenous p21WAF1/CIP1 promoter contributes to transcriptional activation of the p21WAF1/CIP1 in HeLa cells, p21CIP1 mRNA is absent in human T-LBL biopsies and T-ALL cell lines at a high frequency. However, unlike p15INK4B, reduced p21CIP1 expression in T-LBL/ALL is independent of dense promoter-associated CpG methylation, Nuclear clusterin function is proapoptotic in colon cancer when induced by APC or chemotherapy in the context of p21 expression., A significant increase in p21, p53, and fas mRNA expression were reported in the proximal incompetent veins; negative correlation between media apoptotic index and p21 mRNA expression was found., IRF-1-p300 interface as an allosteric modifier of DNA-dependent acetylation of p53 at the p21 promoter, P21waf1/cip1 system alteration may be an early and frequent event in tongue carcinogenesis., c-Myc antagonized the induction of p21Cip1 mediated by oncogenic H-, K-, and N-Ras and by constitutively activated Raf and ERK2, Deletion mutants of p21 promoter reveal that sequences between -270 and -264, forming a complex with unidentified nuclear factor(s), were critical for E2A and Snail function. E2A-dependent expression of endogenous p21 gene was also inhibited by Snail., in tumor cells lacking functional p53 and/or p21, p14(ARF) impaired mitotic entry and enforced a primarily cytoplasmic localization of p34(cdc2) that was associated with a decrease in p34(cdc2) kinase activity and reduced p34(cdc2) protein expression, The cytoplasmic localization of p21,Cip1 may be the molecular mechanism whereby breast cancer cells circumvent TNF-alpha-induced growth inhibition and apoptosis., We conclude that (1) clinically achievable doses of ionizing radiation can trigger CDKN1A-dependent accelerated senescence in some human tumor cell lines that express wild-type TP53., p21WAF expression is induced by 5-Aza-CdR by demethylation of p73 leading to p53-independent apoptosis in myeloid leukemia, differentiation-inducing agents, particularly sodium butyrate, suppress growth of oral squamous carcinoma cells through apoptosis and induce cell differentiation possibly through mechanisms involving COX-2, p27Kip1 and/or p21WAF1/Cip1 in vitro and in vivo, Rb, p21Cip1, and PCNA have roles in cAMP-mediated inhibition of DNA replication and S phase progression, Results demonstrate the importance of posttranslational stabilization of p21 protein by WISp39 in regulating cellular p21 activity., p21Cip/WAF1 induction is a determinant in the regulation of colonic proliferation by the ERK pathway., increased expression leads to increase in apoptosis independent of p53, the mutually antagonistic action of two RNA-binding proteins, Hu and hnRNP K, control the timing of the switch from proliferation to neuronal differentiation through the post-transcriptional regulation of p21 mRNA, p21 is a common target of all TGF-beta superfamily pathways, Among cyclin-dependent kinase inhibitors, p21 was induced and up-regulated by 15d-PGJ(2), but p16 and p27 were not changed, suggesting that the involvement of p21 in inhibition of cell proliferation., results suggest that p21 and FasL gene activation is required for myeloid leukemia cell survival or maturation but not for cell death via Sp1 and NFkappaB as regulators of these genes, low molecular weight forms of cyclin E may contribute to tumorigenesis through their resistance to the inhibitory activities of p21 and p27 while sequestering these CKIs from the full-length cyclin E, Results showed a significant, progressive loss of expression of p21(Cip1/WAF1) with advancing papillary thyroid carcinomas., Mitf-mediated activation of p21Cip1 expression and consequent hypophosphorylation of Rb1 will contribute to cell cycle exit and activation of the differentiation programme, Quercetin and ellagic acid combined increase the activation of p53 and p21(cip1/waf1., Expression of CDKN1A and Gadd45 proteins acting on cell cycle checkpoints and DNA repair in PCa relative to the presence of oxidative DNA damage was measured., pioglitazone generally does not modulate p21 transcription in human cancer cell lines, P21 and Bax have roles in progression of cutaneous malignant melanoma, p21WAF1/CIP1 behaves as a transcriptional coactivator in a gene-specific manner implicated in cell differentiation., Temporal ectopic expression of p21(Cip1) arrested cell proliferation, inhibited Cdk2 and Cdk4 activities, suppressed retinoblastoma phosphorylation and arrested cells in both G1 and G2 cell cycle phases., Lack of functional p21 resulted in the accumulation of cells in G2/M phase of the cell cycle and markedly enhanced p14 ARF-induced apoptosis., Dehydroepiandrosterone increased the expression of p53 and p21 mRNAs., galectin-8 is a modulator of cellular growth through up-regulation of p21, Glioblastoma cells show different and independent responses in their p53 and p21 pathways to ionizing radiation, In the abscence of this this gene in colorectal carcinoma cells, toxicity of histone deacetylase inhibitors was reduced., demonstrated that epigallocatechin-3-gallate activates growth arrest and apoptosis primarily via tumor suppressor p53-dependent pathway that involves the function of both p21 protein and Bax protein, These data implicate p21 as a pivotal macrophage facilitator of HIV-1 life cycle; regulators of p21, such as CDDO, may provide an interventional approach to modulate HIV-1 replication., unable to arrest tumor progression in oral squamous cell carcinoma, Hyperphosphorylated p21 activates the Cdc2 kinase in the G2/M transition., This study suggests that the p21 codon 31 polymorphism does not contribute to the risk of POAG (primary open-angle glaucoma) in the Caucasian population., expression was found to be associated with poorer prognosis and tumor aggressivity in oral squamous cell carcinoma, TP53, CDKN1A, CDKN2A, and CDKN2B have roles in tumorigenesis in skin melanomas, but none of them is a main mutation target for melanoma tumorigenesis, Data show a coordinating inhibition of the proliferation of MCF-7 by enhancing expression of p53,p21 and decreasing expression of c-myc, the mechanism of p21 protection is by direct inhibition of cdk2 activity and that cisplatin-induced apoptosis in kidney failure is caused by a cdk2-dependent pathway, expression of p53, MDM2, and p21Waf1 suggests a role for these oncoproteins in the regulation of endometrioma cell growth, but not in adenomyosis, Significant increase in squamous cell carcinoma of the head and neck in the presence of two p21 polymorphisms may be a marker of genetic susceptibility., physiological concentrations of conjugated linoleic acid inhibit growth of colon cancer cells with either wild-type or mutant p53, In cholesteatoma, co-expression of p21 and pERK1/2 was prominent, whereas in retro-auricular skin there was hardly any co-expression., mitochondrial stress causes resistance to apoptosis through a p21-dependent pathway, The Cyclin-Dependent Kinase Inhibitor p21 plays key roles in cell cycle regulation, and was methylation-negative in myeloid neoplasia., p21cip1/waf1 has a role in growth, apoptosis and differentiation in human colon carcinoma cells, This study using lymphocyte proliferation as a model evaluates the effects of recombinant p21 protein on lymphocyte proliferation, cytokine expression, and the mechanism of antiproliferative effects of p21 in activated lymphocytes., Cdk2 destabilizes p21 via the cy2 cyclin-binding motif and p21 phosphorylation, p300 regulates p63-dependent transcription of p21, There is enhanced G2/M arrest by NF-kappa B-dependent p21waf1/cip1 induction., p21 is one specific target of PR3; PR3-mediated p21 cleavage prevents monocytic differentiation, Results suggested that the overexpression of p21(WAF1/CIP1) in conjunction with the loss of p53 expression was a stronger predictor of survival benefit than either molecule alone in Japanese serous-type advanced ovarian cancer., p73 upregulates p21 transcript abundance (TA) in BC tissues and upregulated p21 TA may result from E2F1 upregulation of p73 but not from E2F1 directly, p53 and p21 act in series in mediating cell cycle arrest. However, the two risk factors, p53 proline homozygosity and p21 arginine allele, although part of a common causal pathway, appear to act in a mutually exclusive manner., Induction of p21WAF1 expression increases tumor cell survival and may result in recurrences at treated sites after cryotherapy., P21(WAF1/Cip1) plays a major role in angiogenesis in breast cancer, since tumor cells seem to down-regulate endothelial p21(WAF1/Cip1), compared to endothelial cells grown in serum-free medium., Sp3 D-domain modulates its protein levels and activation of the p21(CIP1/WAF1) promoter, p53 codon 72 alleles influence the response to anticancer drugs in cells from aged people by regulating the cell cycle inhibitor p21WAF1, PPARdelta partially rescued prostate epithelial cells from growth inhibition and also dramatically inhibited sulindac sulfide-mediated p21WAF1/CIP1 upregulation., increased mRNA stability is the major mechanism of p21(WAF/CIP1/SDI1) elevation in the hydroxyurea-induced growth arrest of human fibroblasts, Overexpression of p21 correlates with chromosomal instability and serves as an adverse prognostic predictor for patients with esophageal squamous cell carcinoma., Tumor suppressor activity of RUNX3 is associated with its ability to induce p21 (WAF1/Cip10) expression., a change of intracellular distribution of p21CIP1 from nucleus to cytoplasm along with differentiation appears to be anti-apoptotic, p21WAF1/CIP1 may have a role in oral tongue squamous cell carcinoma progression, ERK activation and p21 and N-cadherin upregulation are required for genistein-induced neuronal differentiation, KSHV vGPCR expression results in cell-cycle arrest of KSHV-infected PEL cells; it is shown that this arrest is mediated by p21 in a p53-independent manner., p21(CDKN1A) levels after low doses of UV-irradiation may be controlled in a p53-dependent manner without severe reduction., The genesis and invasion of ameloblastoma is associated with the cell proliferation and differentiation, and regulated by the higher expression of cyclin E and the lower expression of p21(WAF1) and p27(KIP1)., These data suggest a physiological role of SREBP-1a in p21 regulation., Basal expression of p21 plays a more important antiapoptosis role than stress-stimulated p21 in carcinoma cells., musashi homolog 1 ability to regulate progenitor maintenance is through the translational inhibition of the cyclin-dependent kinase inhibitor p21WAF-1., In summary, the p53/p21 pathway is mainly responsible for GC-induced apoptosis, but the coordinated activation of the p53/p21 and p16 pathway is responsible for GC-induced endothelial cell senescence through a Rb-dependent mechanism., In addition, the transcription factor Sp1 that is involved in the Ras/ERK-mediated control of p21WAF1 regulation in VSMC in response to PDGF has now been identified., Tax1 induced transcriptional upregula inhibitors p21(cip1/waf1) (p21) and p27(kip1) (p27), and marked suppression of hematopoiesis in immature CD34 cells., Overall, these results suggest that MRPL41 arrests the cell cycle by increasing the p21(WAF1/CIP1) and p27(Kip1) levels under the growth inhibitory conditions., Data demonstrate that ubiquitination of p21(Cip1/WAF1) requires a functional interaction between p21(Cip1/WAF1) and the cyclin E-Cdk2 complex., p21WAF1/CIP1 expression in metastatic prostate cancer cell lines is enhanced as a result of demethylation of the DNA, Checkpoint kinase 1 plays a primary role in the protection of cells from death induced by replication fork stress, whereas p21 mediates through its role in regulating entry into S phase, Results describe the opposite effect of ERK1/2 and JNK on p53-independent p21WAF1/CIP1 activation involved in the arsenic trioxide-induced human epidermoid carcinoma A431 cellular cytotoxicity., Gfi1 associates with G9a and HDAC1 on the promoter of the cell cycle regulator p21Cip/WAF1, resulting in an increase in K9 dimethylation at histone H3, hSNF5 binds the p16INK4a and p21CIP/WAF1 promoters, suggesting that it directly regulates transcription of these genes., The signaling pathway for colonocyte apoptosis following toxin A exposure involves p38-dependent activation of p53 and subsequent induction of p21(WAF1/CIP1), resulting in cytochrome c release and caspase-3 activation through Bak induction., Our results indicate that the TP53 P allele is associated with a worse prognosis (P=0.011) while P21 polymorphism genotypes did not reveal any statistically significant result (P>0.05)., MDM2 has critical roles in the regulation of p21 and E2F1 expression, stability and function [review], p21/WAF1 inactivation may confer a strong resistance to paclitaxel in noncancerous breast epithelial cells harboring a p21/WAF1 mutant., The p21(waf1/cip1) gene is a primary 1alpha,25(OH)2D3-responding gene with at least three VDR binding promoter regions, in two of which also p53 co-localizes., p50 might target or anchor p21 to pol delta complex upon certain DNA damage such as adriamycin treatment., This study demonstrates for the 1st time the involvement of MAPK-cyclin D1-p21(cip)machinery during cell growth inhibition and apoptosis of human vascular smooth muscle cells induced by cysthationine gamma-lyase overexpression., p21(Waf1/Cip1) promoter methylation may be a critical biological barrier to postpone the aging process, The role of histone deacetylases in the expression of CDKN1A in normal and neoplastic human colon cells is reported., These results indicate that early recruitment of p21 protein to DNA-damage sites is a NER-related process dependent on interaction with PCNA, thus suggesting a direct involvement of p21 in DNA repair., LKB1 has the potential to induce p21 expression in collaboration with LMO4, GATA-6, and Ldb1 through the p53-independent mechanism, Subcellular targeting of ING1 by phosphorylation-dependent 14-3-3 binding regulates P21 expression., low doses of Taxol for 18 h determined the upregulation of p53 and p21 waf expression concomitantly with a decrease of the anti-apoptotic Bcl-2., In mammalian cells, translesion DNA synthesis (TLS) is controlled by the tumor suppressor p53, and by the cell cycle inhibitor p21 via its PCNA-interacting domain, to maintain a low mutagenic load at the price of reduced repair efficiency., These data demonstrate a critical role for FAK in the regulation of cyclin-dependent kinase inhibitors (CDKIs) through two independent mechanisms, Pim-1 expression may be regulated by progesterone during mammary development and Pim-1 associates with p21 in mammary epithelial cells, results suggest that inhibition of cell growth by activin is regulated by the negative feedback effect of Smad7 on the activin signaling pathway, and is mediated through p21(CIP1/WAF1) activation in SNU-16 cells, p21-mediated cytoprotection against hyperoxia involves regulation of Bcl-XL and is uncoupled from its ability to inhibit proliferation, BRCA1 could act as a CTD kinase inhibitor and, as such, contribute to the regulation of p21 gene expression, suggest a novel retinoic acid (RA)-signaling, by which RA-induced p21 induction and complex formation with cyclin E/cyclin-dependent kinase 2 (CDK2) diverts CDK2 function from normally driving proliferation to alternatively promoting apoptosis, Loss of a functional mitochondrial electron transport chain inhibits cell-cycle progression, and we postulate that this occurs through the decreased concentration of reactive oxygen species, leading to downregulation of p21CIP1/WAF1., analysis of novel mechanisms for apoptosis induction by silibinin involving p53-caspase 2 activation and caspase-mediated cleavage of Cip1/p21, UV induces p21 degradation through an Skp2 and ubiquitin-independent pathway, In particular, patients with positive p21/high Ki-67 (P = 0.015) or positive p21/negative cyclin D1 (P = 0.04) showed the worst survival outcome., Possible involvement of CDKN1A and CDKN1B variants in the etiology of breast cancer., P21(waf1/cip1) is identified as a target gene of DDX3, and the up-regulation of p21(waf1/cip1) expression accounted for the colony-suppressing activity of DDX3., EGFR-mediated induction of enterocyte proliferation requires MAPK-dependent increase in p21(waf1/cip1) expression in intestinal epithelial cells., Expression of AR protein in PC3-Lenti-AR cells resulted in transactivation of p21 and growth inhibition in culture and in mouse xenografts. Such inhibition was due to induced G1 arrest as documented by expression changes in p27 and p45(SKP2) proteins., expression of either AP-2gamma or AP-2alpha induces p21 and inhibits breast carcinoma cell growth, p53 preferentially occupied the promoters of growth arrest genes p21 and GADD45 in senescent normal human diploid fibroblasts., HDACi induction of the cyclin-dependent kinase inhibitor p21(waf1) has been shown to require ataxia-telangiectasia mutated (ATM)., p21WAF1/CIP1 and 14-3-3 sigma expression was several fold higher in degenerated aortic valves with no calcification versus degenerated aortic valves with calcification on both transcription and translation levels, These data show that specific interaction of the Akt2 isoform with p21 is key to its negative effect on normal cell cycle progression., Klotho normally regulates cellular senescence by repressing the p53/p21 pathway, This novel finding indicated that IKKbeta could mediate cytoplasmic p21 accumulation via activation of its downstream target Akt, which was known to phosphorylate p21 and lead to cytoplasmic localization of p21., RNPC1a is required to maintain the stability of p21 transcript induced by p53., The degradation of p21(WAF1/CIP1) induced by PP2Cgamma was mediated in a proteasome-dependent manner., We find an over-abundance of p21 due to reduced protein turnover, possibly due to the loss of activity of the CSA/CSB E3 ubiquitylation pathway, Risk of cancer is markedly increased in heavy smokers (>20 pack-years) with squamous-cell carcinoma carrying an amino acid substitution., association between locally advanced breast cancer and one particular polymorphism of the p21 gene, p27 is widely expressed in gastric well differentiated endocrine tumors (GWDETs), while p21 expression is sparse and observed in two thirds of the cases. Loss of p21 and p27 expressions may be correlated with different carcinoid tumor subtypes., GAX activates p21WAF1/CIP1 expression in vascular endothelial cells through direct interaction with upstream AT-rich sequences, Dox-induced decrease in KAP1 sumoylation is essential for Dox to induce p21 expression and subsequent cell growth inhibition in MCF-7 cells, p21 gene promoter in combination with a rAAV vector is potentially usable for the development of a low-dose radiation-inducible vector for cancer gene therapy., APMCF1 participates at least partially in cell cycle regulation through regulating genes such as p21 and TIMP3., Results suggest that EGCG may have an inhibitory effect on UVB-induced photo-damage and apoptosis by blocking the cytokine secretion and the mRNA expressions of p53, p21 and c-fos genes., Chromatin immunoprecipitation analyses show that LKB1 is recruited directly to the p21/WAF1 promoter, as well as to other p53 activated promoters, in a p53-dependent fashion., association of Zac1 with importin alpha1 is also involved in regulating the transactivation activity of Zac1 on the p21WAF1/CIP1 gene and protein expression, Identification of a functional target site for the transcription factor, nuclear factor I (NFI), in the basal promoter from the p21 gene., While the DNA replication checkpoint is unlikely to regulate the assembly of a p21 promoter initiation complex, it signals to one or more factors involved in the process of transcriptional elongation., The crucial role of p21Cip/WAF1 in the extracellular signal-regulated kinase pathway-dependent antiproliferative responses by tautomycetin was confirmed by using p21Cip/WAF1 gene-deleted HCT-116 cells., Vpr may regulate HIV-1 gene expression via interacts with the N- and the C-terminal domains of p21., p53 and Ki-67 were expressed with increasing frequency, and bcl-2, p21, and mdm-2 with decreasing frequency in thyroid carcinoma progression. p27 and cyclin D1 were expressed in <15% of cases, with a trend toward decreasing expression., p21 and p27 in carcinoma of oral cavity have roles in progression of squamous cell carcinomas, individual variations in radiosensitivity and in the level of induction of TP53 (and consequently CDKN1A) are congruent, irrespective of the genetic background of the nontransformed fibroblasts, Has important role in mediating the apoptotic effect of histone deacetylase inhibitors., This is the first demonstration of GSK-3beta as the missing link between UV-induced ATR activation and p21 degradation., Loss of p21(WAF1) facilitates AML1-ETO-induced leukemogenesis., PI 3-K signaling pathway suppresses phorbol 12-myristate 13-acetate-induced expression of p21WAF1/Cip1 in human leukemia cells, and that this effect is partly mediated by PKC zeta., p21(WAF1/CIP1) (p21), a negative regulator of the cell division cycle, exhibits proteasome-sensitive turnover and ubiquitination in a tumor cell line., Spider venom activates the expression of p21 and causes selective cell cycle arrest at G(2)/M phase, leading to HepG2 cell apoptosis., p21 plays a key role in mechanisms used by PTEN-deficient tumors to escape chemotherapy, Multiple lines of evidence indicate that the transcriptional process of p21 is downregulated by depressed zinc status in HepG2 cells., CDA1 induces p53- and MEK/ERK1/2 MAPK-dependent expression of p21 by acting through the p53 responsive element in the p21 promoter and this contributes to its antiproliferative activity, Binding of p21(Cip1) to apoptosis signal-regulating kinase 1 (ASK1) requires ASK1 kinase function and may involve phosphorylation of S98, The expression of p21 in the patients with wild-type EGFR tended to be associated with poor overall survival., c-Abl and p53 can be recruited to the region containing p53 binding site of p21 promoter, and c-Abl increases the DNA binding activity of p53 to the p21 promoter, results argue that Mdm2 is needed for full inhibition of Cdk2 activity by p21, thereby positively contributing to p53-dependent cell cycle arrest, study demonstrates that PKCdelta-mediated phosphorylation of 146Ser residue of p21WAF1/CIP1 is a novel mechanism for enhancing the cellular stability of the inhibitor protein by blocking caspase-3-mediated degradation, the RUNX2 and YAP65 interaction has a novel role in oncogenic transformation that may be mediated by modulation of p21(CIP1) protein expression, findings do not suggest mutations or polymorphisms of p21B to play a major role with respect to either breast cancer risk or sensitivity towards chemotherapy, p21 is upregulated after radical prostatectomy for prostatic neoplasms., CARF may exert a vital control on p53-HDM2-p21(WAF1) pathway that is central to the cell cycle control, senescence, and DNA damage response of human cells, stress-induced premature senescence (SIPS) from hydrogen peroxide is associated with a transient increase in DNA-binding activity of p53 and an increased expression of p21(WAF-1) in human hTERT fibroblasts, The down-expression of p21(WAF1) mRNA in colorectal carcinoma might be associated with histone hypoacetylation in chromatin but not with biological behaviors., reactive oxygen species induce p21(Cip1) degradation through an NES-, Skp2-, and ubiquitin-dependent pathway, livers maintained effective removal of cells from the cell cycle by overexpression of p21, adhesion of mantle cell lymphoma and other non-Hodgkin lymphoma cells to bone marrow stromal cells resulted in a reversible G(1) arrest associated with elevated p27(Kip1) and p21 (WAF1) proteins, induction of p21 protects against sulforaphane-induced mitotic arrest in LNCaP cells, immunoreactivity of p53, MDM2, WAF1, and BCL-2 were measured in soft tissue sarcomas cases consisting of 54 low-grade, 40 intermediate-grade, and 58 high-grade sarcomas, fibrillar collagen can also arrest cells at the G2 phase, which is mediated in part by p21(CIP1), a new role for YY1 as both an inducer of p53 instability in smooth muscle cells, and an indirect repressor of p21WAF1/Cip1 transcription, p21WAF1/Cip1-cdk4-cyclin D1 assembly and intimal thickening., ataxia telangiectasia mutated protein phosphorylation of ZBP-89 contributes to HDACi induction of p21(waf1) gene expression, p21 acts as a negative regulator of p53 stability in different cell types and may provide a negative regulatory loop that limits p53 induction., Ski siRNA increased TGF-beta-induced Smad2 phosphorylation and p21 expression., The association of p53 codon 72 and CDKN1A codon 31 polymorphisms with oral cancer risk in a Taiwanese population were investigated., TSG101 negatively regulates p21 levels, and up-regulation of TSG101 is associated with poor prognosis in ovarian cancer, Low expression of p21 was detected but had no effect on survival or recurrence in the univariate analysis., PKC epsilon exerts its oncogenic activity through deregulation of the cell cycle via a p21/Cip1-dependent mechanism, Overexpression of p21/WAF1 is an independent prognostic factor in hepatocellular carcinoma which favors survival., Data show that functional cooperation between TrkA and p75(NTR) accelerates neuronal differentiation by increased transcription of GAP-43 and p21(CIP/WAF) genes via ERK1/2 and AP-1 activities., Rhabdomyosarcoma cells overexpressing MDM2 abrogated ceramide-mediated p21(Cip1/Waf1) induction, G(2) arrest and the late ensuing apoptosis., Histone deacetylase inhibitors enhance lexatumumab-induced apoptosis via a p21Cip1-dependent decrease in survivin levels, Elevated expression of cell-cycle regulators p16(INK4A), p21(CIP1), and cytoplasmic/nuclear beta-catenin correlated with increased colorectal cancers risk, as did elevated expression of survivin and human telomerase reverse transcriptase., p21WAF1/CIP1 is a common transcriptional target of retinoid receptors RAR and RXR, Downregulation of caveolin-1 expression affects bleomycin-induced cell cycle arrest and subsequent cellular senescence that is driven by p53 and p21., Upon DNA damage, histone H2A.Z is first evicted from the p21 promoter, followed by the recruitment of the Tip60 histone acetyltransferase to activate p21 transcription., type I IFN prolongs cell cycle progression by p21WAF1/CIP1 induction in human colon cancer cells, Treatment with Magnolia plant extracts upregulated epression of this protein in a bladder cancer cell ilne., Data indicate that overexpression of the transcriptional cofactor FHL2 contributes to breast cancer development by mediating transcriptional activation of MAPK target genes known to be involved in cancer progression, such as p21., ectopically BRCA2-expressing cells have different intracellular levels of Aurora A, Aurora B, p21, E2F-1, and pRb, suggesting a BRCA2-mediated suppression of polyploidy via stabilization of the checkpoint proteins levels, The apoptogenic activity of BM-ANF1 was mediated through p53 tumor-suppressor gene expression followed by the expression of p21(Cip1) and p27(Kip1)linking it with cell cycle arrest at G1 phase in cancer cells., Study reports that p18(Hamlet) can also mediate the cell cycle arrest induced in response to gamma-irradiation, by participating in the p53-dependent upregulation of the cell cycle inhibitor p21(Cip1) (CDKN1A)., Data show that knockdown of p21Cip1, but not p16(INK4a) or Rb, allows cells to bypass premature senescence that is induced by BS69 knockdown., 15-48 aa region of p21 is essential for basal expression by preventing degradation by the proteasome, p21Cip1/WAF1 can be phosphorylated by Pim-1 kinase in vitro, implying that part of the function of Pim-1 might involve influencing the cell cycle., TLX recruits histone deacetylases to repress transcription of p21(CIP1/WAF1) and pten and regulate neural stem cell proliferation, Results found that the activation of p21 is primarily by HNF4alpha1 interacting with promoter-bound Sp1 at both the proximal promoter region and at newly identified sites in a distal region (-2.4 kb)and does not need direct DNA binding by HNF4alpha1., Nuclear accumulation of p21 accompanied by accelerated senescence may be an integral component of the response of human fibroblasts to UVC-induced DNA damage, irrespective of their DNA repair capabilities., Our results point to an antiproliferative function of the unliganded ER alpha through its physical interactions with p21(WAF1) that may also explain the favorable prognosis of ER alpha-positive breast cancers., Both PD98095 and dicoumarol were capable of blocking TNFalpha production but had only a small effect on p21Waf1 expression, cell cycle inhibitor p21Waf1/Cip1 genes were found significantly upregulated in the cases with progressive sarcoidosis, that Rac1 is an essential player for mediating the induction of cyclin D1 and p21(Cip1) by HRG in breast cancer cells, There were no apparent differences in immunostaining for p21 in myomas or in normal myometrium, The combination of p53 and p21 expressions in biopsy findings can thus predict the histological effectiveness of hyperthermochemoradiotherapy., ERK activation with some other pathway(s), activated through the HGF receptor, are required to up-regulate p16 and p21 expression, that of p21 contributes to suppression of Cdk2 activity leading to inhibition of proliferation of HGF-treated HepG2 cells., p21 has an important role in the cellular response to normal replicative stress and its absence leads to a "chronic DNA damage" state that primes the cell for p53-dependent apoptosis., the ability of Tbx2 to repress the p21 gene is enhanced in response to a stress-induced senescence pathway, which leads to a better understanding of the regulation of the anti-senescence function of Tbx2., levels of p53/p21waf1 mRNA in blood lymphocytes collected before chemotherapy may predict the chemoresponses of lung cancer patients., Results suggest that a combined analysis of three P21 polymorphisms might better predict the risk of lung cancer than the analysis of a single polymorphism., TP53 Arg72Pro polymorphism, but not p73 G4C14>A4TA4 and p21 Ser31Arg, contribute to risk of cutaneous melanoma, The culture of cells in the Cl(-)-replaced medium significantly increased expressions of p21 mRNA and protein without any effects on p53., Orphan nuclear receptor estrogen-related receptor-beta suppresses in vitro and in vivo growth of prostate cancer cells via p21(WAF1/CIP1) induction., These results demonstrate that MDMX and MDM2 independently and cooperatively regulate the proteasome-mediated degradation of p21 at the G(1) and early S phases., linear relationship and prognostic role of the p53/p21/PCNA pathway in gastrointestinal stromal tumors. Abnormalities of the p53/p21WAF1 pathway lead to increased proliferating states, thereby triggering the progression of GISTs., The expression of p21(WAF1/Cip1) and p27(Kip1) was increased at both protein and mRNA levels by hydroxytyrosol, a main phenol of olive oil., discrete PKCs trigger distinctive responses when activated in different phases of the cell cycle via a common mechanism that involves p21 Cip1 up-regulation., loss of p21's cyclin-dependent kinase inhibitory property results in hyperphosphorylation of estrogen receptor-alpha, with subsequent increased gene expression of estrogen receptor-regulated genes, These results imply that HIF-1alpha functions as an up-stream player in the p21-mediated growth arrest of keratinocytes., p21Cip1 is prominent within the dentate gyrus and restricted to the subgranular zone of the developing transgenic p21-deficient mouse dentate gyrus, where it might act to restrain neurogenesis., We immunohistochemically analyzed the expression of p21, p27, p14, p16, p53 and proliferation marker Ki67, in 67 low and high grade astrocytic tumors., the -KTS-containing variants of WT1 are directly involved in the regulation of p21(Waf1/Cip1) expression and the subsequent suppression of lymph node metastasis in human lung squamous cell carcinoma, Reduced expression of p21 could be a helpful diagnostic marker and may contribute to the invasive phenotype of Small-cell neuroendocrine carcinoma of the uterine cervix., p21 is a direct target of miR-106b. Its silencing plays a key role in miR-106b-induced cell-cycle phenotypes., PUMA exerts a negative feedback on p53 and p21, leading to p21-dependent growth suppressive and survival changes., Our results indicate that nicotinamide treatment attenuates p21WAF1 expression through Sp1 downregulation, and suggest a possible involvement of nicotinamide metabolism in cellular gene expression., We propose that BARD1 reduces BRCA1 transcriptional activity, and that this at least partly involves BRCA1/BARD1 E3 ubiquitin ligase activity, which is disrupted by the C61G mutation., present study did not demonstrate a significant association between P21 / WAF1 genotype and oral squamous cell carcinoma, intracellular accumulation of P21WAF1 may be one of the mechanisms which contribute to cigarette smoke extract-induced inhibition of cell proliferation, Defective p53 signaling in p53 wild-type tumors attenuates p21waf1 induction and cyclin B repression rendering them sensitive to Chk1 inhibitors that abrogate DNA damage-induced S and G2 arrest., CARF exerts a vital control on the p53-HDM2-p21WAF1 pathway that is frequently altered in cancer cells., the p21G251A polymorphism significantly correlates to the subgroup of locally advanced breast cancers (p = 0.0049), ERK and JNK MAPK/Elk-1/Egr-1 signal cascade is required for p53-independent transcriptional activation of p21(Waf1/Cip1) in response to curcumin in U-87MG human glioblastoma cells, p16(INK4a), p21(WAF1/CIP1), p27(KIP1), and p53 are expressed in human corneal endothelial cells despite donor ages., BAF180 suppresses tumorigenesis, at least in part, through its ability to regulate p21., variations in c-myc and p21(WAF1) expression delay apoptosis making PBL resistant to sodium butyrate for several hours, High zinc status in normal bronchial epithelial cells upregulates p53 expression which in turn elevates p21, inducing G2/M blockage., Report overexpression of cyclin D1, D3, and p21 in renal carcinomas with Xp11.2 TFE3-gene fusion., CDKN1A expression increased with increasing grade in meningiomas., results support Killin as a missing link between p53 activation and S phase checkpoint control designed to eliminate replicating precancerous cells, should they escape G(1) blockade mediated by p21., S100/A11 and p21 gene expression was also found to be significantly lower in acute and chronic atopic dermatitis skin., Mutations of K-ras and overexpression of the ras p21 were detected in 11% and 76% of the colorectaltumors, respectively, disruption of the spindle-assembly checkpoint does not directly influence p53 activation, but the shortening of the mitotic arrest allows cyclin E-CDK2 to be activated before the accumulation of p21(CIP1/WAF1)., Genistein induces the expression of tumor suppressor genes p21 (WAF1/CIP1/KIP1) and p16 (INK4a) with a concomitant decrease in cyclins in prostate cancer cells., increased expression of p21(Waf1/Cip1) and several other p53-regulated genes is caused by diminished Pdcd4 expression, p21, acting as a sensor of cellular stress, may have potent and wide roles in lung responses triggered by cigarette smoke. [REVIEW], Zbtb4 associates with the Sin3/histone deacetylase co-repressor and represses expression of P21CIP1 as part of a heterodimeric complex with Miz1., oxidative stress-induced expression in biliary epithelial cells in primary biliary cirrhosis is associated with activation of the ATM pathway, Cdc6 determines utilization of p21(WAF1/CIP1)-dependent damage checkpoint in S phase cells, S100A11 targets Rad54B to sites of DNA DSB repair sites and has a role in p21-based regulation of cell cycle, Genetically programmed cell death is related the p21 and p27 pathways in pseudophakic bullous keratopathy., haem oxygenase-1 plays a central role in NNK-mediated cell proliferation by promoting the expression of p21(Cip1/Waf1/Cid1), inhibitor of apoptosis protein 2 and B-cell lymphoma-2 but inhibiting the activity of Bad, crucial role exerted by p21Cip1/WAF1 in PPARgamma action in thyroid neoplasm, Our study has identified p21 protein expression as important biological marker which may indicate the progression of laryngeal squamous cell carcinoma., The combined phenotype of RHAMM and p21 expression is an invaluable independent prognostic immunohistochemical profile in microsatellite instability-high colorectal cancer., The procyanidin-mediated induction of apoptosis and cell-cycle arrest in esophageal adenocarcinoma cells is not dependent on p21(Cip1/WAF1)., p21 could be a potential mediator of survivin suppression at the transcriptional level, Simultaneous knock-down of both p21 and p27 significantly enhanced doubling time, clonogenicity and cell cycle progression in a prostate cancer cell line., Activation of protein kinase G Increases the expression of p21CIP1, p27KIP1, and histidine triad protein 1 through Sp1., Andrographolide inhibits human colorectal cancer Lovo cell growth by G1-S phase arrest and inducing the expression of p53, p21 and p16., HDAC4 is a novel regulator of colon cell proliferation through repression of p21, Zac1 might be involved in regulating the p21(WAF1/Cip1) gene and protein expression through its protein-protein interaction with p53 and HDAC1 in HeLa cells., Deletion of NLS motifs resulted in failure of ING1b to completely localize to the nucleus and inhibited its ability to induce p21WAF1 expression., Radix notoginseng extracts may inhibit the proliferation and promote the apoptosis of precancerous gastric cells through altering expressions of the bcl-2, Bax and p21WAF1 genes., p21 might play an important role in chemosensitivity to anticancer agents, CDK inhibitor p21 is degraded by a proliferating cell nuclear antigen-coupled Cul4-DDB1Cdt2 pathway during S phase and after UV irradiation, Sodium butyrate could induce G1 arrest and inhibit cell proliferation in AGS cells by up-regulating the expression of p21., experiments showed that p21 deficiency in stromal fibroblasts accelerates breast tumor growth through cell non-autonomous mechanism(s); propose that p21 regulation is intimately linked with the ability of stromal cells to affect tumor growth, The p53-dependent transcriptional regulation of p21 in response to DNA damage by ultraviolet radiation and ionizing radiation compared., These results shed light on the molecular mechanism of action of GHRH antagonists in tumor tissues and suggest that the antineoplastic activity of GHRH antagonists could be considered for the treatment of cancers expressing p21., the analysis of p21cip1, p27kip1, and p16INk4a by immunohistochemistry could be useful in the management of patients with papillary thyroid carcinoma, p21 is a negative regulator of PCNA-pol eta interaction., The C/C genotype of p21 may reduce the risk of epithelial endometrial cancer., Increased expression of p21/WAF/Cip1 in primary leukemic blasts suggests that elevated p21/WAF/Cip1 levels may contribute to specific features observed in AML1-positive leukemia., positive expression rate and co-expression rate of P21WAF1/CIP1 and P16 proteins could reflect the malignant grade of glioma to some extent, and they can be considered as a sensitive index for glioma grading, PCNA promotes the ubiquitylation and degradation of the CDK inhibitor p21 in cells irradiated with low dose of ultraviolet radiation, defines the degradation of p21 as a critical aspect of replication licensing in human cells, p21(WAF1/CIP1) is an important factor in the sensitivity of cells to the growth inhibiting and apoptotic effects of OSU03012., Cooperative effect of p21Cip1/WAF-1 and 14-3-3sigma on cell cycle arrest and apoptosis induction by p14ARF, AP4 directly repressed p21 by occupying four CAGCTG motifs in the p21 promoter via its basic region., Tbx2 and Tbx3 may play a dual role during the radial to vertical growth phase transition by both inhibiting senescence via repression of p21(CIP1) expression, and enhancing melanoma invasiveness by decreasing E-cadherin levels., p21 mRNA expression in vinyl chloride exposed workers was significantly higher than in nonexposed workers., HDAC4 interacts with Sp1, binds and reduces histone H3 acetylation at the Sp1/Sp3 binding site-rich p21(WAF1/Cip1) proximal promoter, suggesting a key role for Sp1 in HDAC4-mediated repression of p21(WAF1/Cip1)., knockdown of endogenous MBP-1 is involved in cellular senescence of HFF through p53-p21 pathway., Results indicate that both p16(INK4a) and p21(WAF1/CIP1) are required for the opioid growth factor (OGF)-OGF receptor axis to inhibit cell proliferation in normal cells., CDKN1A/p21 appears to be an essential target of miR-17-92 during B-cell lymphomagenesis, which suggests the miR-17-92 polycistron has distinct targets in different B-cell lymphoma subtypes., protects against oxidative stress by suppressing ER-dependent activation of mitochondrial death pathways, TsA markedly down-regulated the expression of cyclin D1 and CDK4, up-regulated the expression of p21WAF1 and p53 and induced cell cycle arrest at the G1 phase in MCF10A-ras cells, Absence of p21 expression is associated with biologically less aggressive phenotypes in gallbladder and extrahepatic bile duct cancer., Compounds which attenuate p21 cause renal cell carcinoma cell apotosis and sensitize these cells to DNA-damaging chemotherapy., Monocytic leukemia zinc finger (MOZ) interacts with p53 to induce p21 expression and cell-cycle arrest., Gene and protein expression of p53 and p21 in fibroadenomas and adjacent normal mammary tissue., a mechanistic link between JNK activity and liver cell proliferation via p21 and c-Myc and suggest JNK1 targeting can be considered as a new therapeutic approach for HCC treatment., Bortezomib arrests the proliferation of hepatocellular carcinoma cells HepG2 and JHH6 by differentially affecting p21 level., Expression of cyclin E could not predict survival in patients with gastric cancer, whereas the expression of pRb and p21 was associated with a favorable prognosis., Notch-1 may be mediated through regulating the expression of cell cycle regulatory proteins cyclin D1, CDK2 and p21 and the activity of Akt signaling, These results showed that the expression of cyclin D1, p21 and p27, alone or in combination, are early events in gastric tumorigenesis and may serve as a candidate molecular marker for the early gastric carcinoma., After treatment of HepG2 cells with DOX, the expression of p53 and p21 was increased, whereas that of survivin was reduced during 24 hours of the treatment., These results highlight the role of p21 in counteracting inappropriate proliferation stimuli for genome stability maintenance., 1alpha,25-dihydroxyvitamin D(3) regulates p21 transcription by inducing cyclical chromatin looping that depends on both histone deacetylation and demethylation., hCASK regulation of cell growth might involve p21 expression, and that the bHLH (basic helix-loop-helix) transcription factor E2A probably participates in hCASK regulation of p21 expression, vIRF-3 antagonized IRF-5-mediated activation of the p21 promoter., The PKCalpha-ERK1/2 cascade is involved in PMA induced up-regulation of cyclin D1 and P21(cip1) and proliferation in human airway smooth muscle cells., Results describe thet role of P53/P21 and RUNX 3 in the effects of 5-Aza-2'-deoxycytidine on human cancer cells., The results provide support for a model whereby p21 downregulation promotes vinblastine-induced apoptosis by alleviating its protective function following mitotic arrest., The p21 codon 31*C- and DRD2 codon 313*T-related genotypes/alleles, but not XRCC1 codon 399, hOGG1 codon 326, and DRD1-48 polymorphisms, are correlated with the presence of leiomyoma., Oxidative Stress Increases the Number of Stress Granules in Senescent Cells and Triggers a Rapid Decrease in p21waf1/cip1 Translation.(, Data demonstrate that the long-term suppression of Plk1 increases the levels of cyclin-dependent kinase inhibitor p21(WAF1/CIP), which is partially induced by the elevated tumor suppressor p73 in p53-inactivated HeLa cells., reveal a pivotal role for alphaCP1 and alphaCP2 in a p53-independent pathway of p21(WAF) control and cell cycle progression, Emi1 down-regulation and APC activation leads to stable p21-dependent G2 arrest after DNA damage., nucleophosmin as a positive post-translational regulator of p21., RASSF1A can mediate cell cycle arrest and senescence in human cancer cells by p53-independent regulation of p21(Cip1/Waf1)., Results suggest that loss of IKKbeta activation is important for the enhancement of p53 stability, leading to p21 expression and cell cycle arrest and apoptosis of tumour cells., MDM2 released from p53 by RITA promotes degradation of p21 and the p53 cofactor hnRNP K, required for p21 transcription, Study concludes that the minor allele A at -899 of CDKN1A is associated with increased susceptibility to systemic lupus erythematosus and lupus nephritis, and decreased cellular levels of p21., Data show that the growth inhibitory effects of the glyceollins appeared to be due to an inhibition of G1/S progression and correlated with an up-regulation of cyclin-dependent kinase inhibitor 1 A and B mRNA and protein levels., increases of p16(INK4a) and p21(WAF1/cip1) expression in response to BMP4 were mediated by the Smad1/5/8 signaling pathway., Results establish a new role for H2AX in the p53/p21 pathway and indicate that H2AX is required for p21-induced cell cycle arrest after replication stalling., p21(WAF1)-p300-DNMT1 pathway may play a pivotal role to ensure regulated DNMT1 expression and DNA methylation in mammalian cell division., p31(comet) induces tumor cell senescence by mediating p21(Waf1/Cip1) accumulation and Mad2 disruption and that these effects are dependent on a direct interaction of p31(comet) with Mad2., Data provides a novel mechanism for transcription activation by FOXP3 and a genetic mechanism for lack of p21 in a large proportion of breast cancer., p21(Cip1/WAF1) overexpression is an excellent favorable prognosticator in tonsillar squamous cell carcinomas, Results indicate that degradation of p21 is not dependent on a particular DNA repair pathway, and is not required for efficient DNA repair., SHP induced the cell cycle regulatory protein levels and cooperatively increased an induction of p21WAF1 expression with p65., An inhibition of cell proliferation associated with upregulation of p21(Cip1/WAF1) was observed following transfection of DUOXA1, Diesel particle-induced transcriptional expression of p21 involves activation of EGFR, Src, and Stat3, The Bax activator BimEL increased rapidly, driving cells towards apoptosis likely controlled by c-Myc and p21(WAF1) activities., The degradation of p21(Cip1) and other targets of the Cul4-DDB1(Cdt2) E3 ligase may collectively contribute to the survival of neoplastic cells after ionizing radiation., Tax increases p21 mRNA expression by transcriptional activation and mRNA stabilization, ERK2 activation transduces mitogenic signals, at least in part, by downregulating the cell cycle inhibitory protein p21(Cip1)., ectopic Meox2 suppressed epithelial cell proliferation in cooperation with TGF-beta1, and mediated induction of the cell cycle inhibitor gene p21., dsRNA mediated gene activation is demonstrated in renal cell carcinoma and suggests that forced over-expression of p21 may lead to an increase in apoptosis through a survivin dependent mechanism, The observations suggest that p21(WAF1) plays a role in mediating replication of oncolytic viruses with potential implications for adenoviral therapy of cancer., Letter, NORE1A activates p21(CIP1) via promoting p53 nuclear localization., The expressions of p53, p21 and Ki67 proteins are closely related with the pathogenesis and progression of nasal NK/T-cell lymphoma., Results suggest that adenovirus-mediated transduction of p53 and p21-specific microRNAs may be useful for gene therapy of human cancers., the expression of p53, p21 and RB was not significantly different in penile verrucous carcinoma than in usual type squamous cell carcinoma., inactivation of p21(WAF1/CIP1) checkpoint function occur in low-grade dysplastic lliver nodules as well as in high-grade liver dysplastic nodules in patients with chronic B viral cirrhosis, Cyclosporine A inhibits colorectal cancer proliferation probably by regulating expression levels of c-Myc, p21(WAF1/CIP1) and proliferating cell nuclear antigen., ablation of the protein kinase Chk1 rescues the p21 transcription elongation defect when cells are blocked in S phase, describes a third abnormal response pattern characterized by failure of p21 protein accumulation despite a normal p53 protein response, ZBTB5 directly repressed transcription of cell cycle arrest gene p21 by binding to the proximal GC-box 5/6 elements and the two distal p53-responsive elements (bp -2323 to -2299; bp -1416 to -1392), TheCyclin-Dependent Kinase Inhibitor p21 cooperate to determine sensitivity to DNA damage following chk 2 inhibition and that chk 2 modulates the biological rheostat that determines whether a cell undergoes arrest versus death., polymorphisms in p21 may be protective against the risk of chronic benzene poisoning in the Chinese occupational population., Combination of p53 expression and p21 loss has an independent prognostic impact on sporadic colorectal cancer., Data show that inhibition of p38 MAPK and its phosphorylation of HuR impairs p21(Cip1) accumulation and, as a result, the ability of cells to arrest in G(1) in response to gamma radiation., Data indicate that MKRN1 is a novel modulator of p53 and p21, preferentially leading cells to p53-dependent apoptosis by suppressing p21., PP2Cgamma is a novel regulator of p21(Cip1/WAF1) protein stability via the Akt signaling pathway., results provide evidence for a new regulatory loop involving the NER protein DDB2, Mdm2, and p21(Waf1/Cip1) that is critical in deciding cell fate (apoptosis or arrest) upon DNA damage., Data show that DADS induces G(2)/M arrest in colon cancer SW480 cells, probably through the downregulation of PCNA, p53 and cyclin B1 and upregulation of p21(WAF1)., over-expression of DIXDC1 might target p21 and cyclin D1 to promote colon cancer cell proliferation and tumorigenesis at least partially through activation of the PI3K/Akt pathway., study found no link between polymorphisms in APOE, p53, and p21 genes and primary open-angle glaucoma in Turkish patients,although a larger sample is required to elucidate the role of these polymorphisms in the pathogenesis and course of glaucoma, CTIP2 is a constitutive p21 gene suppressor that cooperates with SUV39H1 and histone methylation to silence the p21 gene transcription., Among human cancers, sebaceous carcinoma of the eyelid may be one of those showing most frequent mutation of the p53 gene, which may not be caused by exposure to UV. p21(WAF1/CIP1) downregulation may be associated with lymph node metastasis., Data show that NTD upregulated the expression levels of apoptosis related genes p53, BAX and p21 in A549 cell line., These data clearly demonstrate that ITF-2A regulates CDKN1A transcription., The increased levels of p53 in post-selection human mammary epithelial cells are due to the presence of an Mdm2 fragment that binds p53 but does not result in its degradation., In several paired samples before and after F-refractory disease, no change in p21/p53 induction was observed after DNA damage., zinc deficiency differentially modulated the Akt-Mdm2-p53 signaling axis in normal prostate cells vs. the Akt-p21 signaling axis in malignant prostate cells., down-regulation of p21 was strongly associated with HPV-18 positive cervical carcinomas, P21WAF1 protein may be related to the malignant development of epithelial ovarian cancer. CDK1 expression was negatively correlated to P21WAF1 expression., ROCK-mediated up-regulation of p21(Cip1) and the cytoskeleton in PKCdelta-dependent apoptosis in prostate cancer cells., the homeodomain-interacting protein kinase-2 (HIPK2) and p53 were found activated along a pro-apoptotic signalling pathway while p21(waf1,cip1,sdi1) was prevented from its protective action, Immunoreactivity index of p21 and cyclin D1 is independent of the morphological pattern of human endometrium, patients' age and gynaecological history of patients., APPL1 overexpression affects the composition of the HDAC1-containing NuRD complex and the expression of HDAC1 target p21WAF1/CIP1, JNK activation is involved in the terbinafine-induced inhibition of ERK phosphorylation, p53 and p21 up-regulation and DNA synthesis inhibition in HUVEC, regulation of p21 intracellular distribution is a new mechanism for BCCIP to modulate p21 functions, Data show that the inhibition of cell proliferation with L.lac CF was associated with an increase in p53 and p21 expression, the reduction of cyclin D1 expression, and retinoblastoma protein phosphorylation., Data show that kidney bean husk extract exhibited antitumor effects accompanied by the increase in p-AMPK and p-Acc as well as antitumor proteins p53 and p21., Androgen via p21 inhibits tumor necrosis factor alpha-induced JNK activation and apoptosis, Data show that Protein levels of tumor suppressor targets of the miRNAs were increased by antisense to miR-21 (PTEN and RECK) and miR-221 (p27)., p21(WAF1) can induce thioredoxin secretion and angiogenesis in cancer cells, by direct transcriptional repression of the thioredoxin-binding protein 2 promoter, Fndings suggest that the selected polymorphisms of p21, CCND1, and caspase8 may not contribute to the risk of colorectal cancer., AP-2gamma promotes proliferation in breast tumour cells by direct repression of the CDKN1A gene., Chondrocytes in cartilage biopsies of ACH children were characterized by the presence of growth arrest mediated by STAT(signal transduction and transcription) activation and increased expression of p21(p21CIP1) and cyclin D1, Growth-inhibitory effect of let-7a on the A549 cells in vitro and in vivo may be explained in part by le-7a-induced suppression of NIRF and elevation of p21(WAF1)., analysis of BMP-4 induction of arrest and differentiation of osteoblast-like cells via p21 CIP1 and p27 KIP1 regulation, P21 Codon 31 with AGA (Arg) allele is a genetic risk factor of cervical squamous cell carcinoma., Data suggest thta MST kinases 1/2 serve to monitor cytoskeletal integrity and couple the JNK1/SAPK1 pathway to the regulation of the cell cycle regulatory protein p21Waf1., Expression of P-gp was reduced along with increasing concentration of tetrandrine in K562 cells., This study shows that the activation of the p53-p21(Cip1/WAF1) pathway acts as a major mediator of cellular senescence induced by CKII inhibition., increase in CDK6, Cyclin E, p27kip1, and p21waf1 expression, and after 6BIO treatment, the expression of most of these proteins decreased., These data together show that p21 translocates to the nucleus to participate in DNA repair, while the rest is rapidly degraded in the cytosol., Results indicate that the p21 polymorphism may contribute to susceptibility to pancreatic cancer, particularly among p27 homozygous wild-type carriers and nonsmokers., Loss of cip1 protein is associated with intravesical recurrence following transurethral resection in in non-muscle-invasive bladder cancer., Expression of cyclin D1 and P21WAF1 is related to drug-resistance of gastric cancers., Using the chi square test ( table 2 ) the expressions of GST-pi (p = 0.003), Neu/Her-2 (p = 0.017), and p21 (p = 0.034) in cardiac cancer were significantly higher than those in distal gastric cancer., effects of progesterone metabolites on cell proliferation, mitosis, apoptosis and expression of Bcl-2, Bax and p21, Data suggest that wogonin induced G1 phase arrest in HeLa cells by modulating several key G1 regulatory proteins, such as Cdk4 and cyclin D1, as well as up-regulation of a p53-mediated p21Cip1 expression., Genetic polymorphisms of p21 is associated with second primary malignancy in patients with index squamous cell carcinoma of the head and neck.(, p21Waf1/Cip1 cleavage, which is mediated by caspase-3 activity, is involved in roscovitine-induced apoptosis, The antioxidant quercetin inhibits cellular proliferation via HIF-1-dependent induction of p21WAF., stimulatory effect of deltaEF1 on cell proliferation through p21 regulation is supported by an inverse correlation of deltaEF1 and p21 expressions in breast cancer cell proliferation., hGTSE-1 mediated-p21(CIP1/WAF1) stabilization is clearly involved in the ability of cells to counteract cytotoxicity induced by the microtubule poison paclitaxel., The proteins p53, p21/WAF1, and MDM2 were overexpressed in all the hepatocellular carcinoma cases in this study., Report roles of p16(INK4A) and p21(WAF1) in replicative senescence and ionizing radiation-induced accelerated senescence in human normal, ataxia telangiectasia and Li-Fraumeni syndrome fibroblast strains., Data show that upregulation of Spry1 in HUVECs inhibits tube formation and is associated with decreased proliferation and increased expression of p21 and p27., HDM4 is overexpressed in mantle cell lymphoma and, at least in part, exerts its effect by suppressing p21 expression, thereby enhancing cell-cycle progression., The p21 gene is a known transcriptional target of MITF, the reciprocal stimulation of transcription may constitute a positive-feedback loop reinforcing MITF expression in melanoma cells., there is a p53-independent function of MTA1 in DNA damage response via modulation of the p21 WAF1-proliferating cell nuclear antigen pathway, This study provides the first demonstration that TSPYL5 modulates cell growth and sensitization of cells to the detrimental effects of damaging agents via regulation of p21(WAF1/Cip1) and PTEN/AKT pathway., p300 has a direct role in the control of cell growth and differentiation in primary epithelial cells, and p21(Waf1/CIP1) is an important mediator of these p300 functions, Overexpression of all these miRNAs rescues HMECs from Ras(G12V)-induced senescence by prevention of Ras(G12V)-induced upregulation of p21(Waf1/Cip1)., Single nucleotide polymorphism in CIP1 gene is associated with esophageal cancer., in comparison of Italian centenarians and younger subjects, rare alleles of 2 exon-derived SNPs, rs1801270 and rs1059234, were under-represented in centenarians; these alleles may be detrimental to longevity and therefore are rare in centenarians, The variance in gene p21 a statistically significant association between the SNP measured within p21 and breast cancer status was observed., Transcriptional regulation of p21/CIP1 cell cycle inhibitor by PDEF controls cell proliferation and mammary tumor progression, EBER1 inhibits p21cip1/waf1 transcription and prevents apoptosis through down-regulation of p53, EGR1, and STAT1., the NH2-terminal FATS physically interacts with histone deacetylase 1 (HDAC1) to enhance the acetylation of endogenous p21, leading to the stabilization of p21., Results show long-term activation of the checkpoint gene CDKN1A (p21) induces mitochondrial dysfunction and production of reactive oxygen species (ROS) through serial signalling through GADD45-MAPK14(p38MAPK)-GRB2-TGFBR2-TGFbeta., The studies indicate that neither expression of p21 protein nor that of viral NS3 protein can serve as a marker of progression of CH-C to HCC in vivo., No significant differences in protein expression patterns or polymorphisms of CDKN1A in relation to the three types of central nervous system tumors were observed among Brazilian subjects., both p21(CIP1/WAF1) and p16(INK4A) are targets for hSNF5 and that p21(CIP1/WAF1) upregulation during hSNF5-induced G(1) arrest precedes p16(INK4A) upregulation., NPAT is essential for histone mRNA 3' end processing and recruits CDK9 to replication-dependent histone genes., multiple miRNAs that can suppress p21Cip1/Waf1 expression by directly targeting its 3' untranslated region, Gfi-1 is recruited to CDKN1A core promoter through Miz-1 and represses CDKN1A transcription., The transfer of p21(waf1) and p27(kip1) genes could inhibit the growth of human breast carcinoma cells and the unnormal duplication of centrosomes., Binding of G-1 compound to GPR30 in PC-3 prostate cancer cells is followed by sustained activation of Erk1/2 and a c-jun/c-fos-dependent upregulation of p21, resulting in the arrest of PC-3 growth at the G(2) phase., high p21waf-1 or tsp-1 mean expression level comprised small-sized, low-grade, node-negative ductal breast carcinomas, The water extract of the lettuce Lactuca sativa activated checkpoint kinase 2, induced the tumour suppressor p21, and downregulated the proto-oncogene cyclin D1 in HL-60 leukaemia cells and MCF-7 breast cancer cells, The anti-tumor mechanisms of genistein may be related with the down-regulation of expression of VEGF and PCNA, and up-regulation of the expression of p21., These data demonstrate that miR-K1 represses the expression of p21, a protein with known tumor suppressor functions, and suggest that this human herpesvirus 8 miRNA is likely to contribute to the oncogenic potential of this virus., p21Waf1/Cip1 gene expression is induced in estrogen responsive MCF-7 breast cancer cells and Sp1 is involved in the recruitment of ERa to the p21Waf1/Cip1 promoter., p21 regulates the interaction between PARP-1 and base excision repair factors, to promote efficient DNA repair., MDM2 promotes proteasomal degradation of p21Waf1 via a conformation change, Nucleolar disruption ensures nuclear accumulation of p21 upon DNA damage, Meta-analysis suggests that the p21 Ser31Arg polymorphism may be associated with breast cancer development in Caucasian., overexpression of p21/WAF1 in osteosarcoma might be one of the poor prognostic factors., Results suggest that p400 represses basal p21 gene expression through dual mechanisms that include direct inhibition of TIP60 and ATP-dependent positioning of H2A.Z at the promoter., CDKN1A functional polymorphisms may contribute to the risk of colorectal cancer in Turkish, The expressions of P53, P21 and Ki67 proteins are closely related with the pathogenesis and progression of nasal NK/T-cell lymphoma., Data support persistent, p53-independent, p21Cip1 induction as a critical mediator of methylselenic acid-induced G(1) arrest in prostate cancer cells., Using HCT116 somatic knockout cells we show that mechanistically premature APC/C activation depends on p53 and its transcriptional target p21 that mediates the signal through downregulation of the APC/C inhibitor Emi1., ID1 enhances docetaxel cytotoxicity in prostate cancer cells through inhibition of p21, Data show that in the presence of a functional p53/Puma/Bax-signaling axis, p14(ARF)-triggered apoptosis is enhanced by loss of p21(CDKN1)-mediated cell cycle checkpoint control., two spontaneously transformed human oral keratinocyte lines from adult human gingival samples revealed a mutation in the p53 gene, loss of p21WAF1/Cip1 and overexpression of p-Rb-Ser807, These two p21 polymorphisms, both alone and in combination, are not genetic susceptibility biomarkers for esophageal squamous cell carcinoma. Interaction with cigarette smoking may influence the susceptibility to ESCC development in northeastern Iran., data suggest low CDKN1A expression in adult T-cell leukemia/lymphoma cells may influence leukemogenesis; abnormal methylation may influence expression of HTLV-1 Tax and also CDKN1A during long-term development of ATLL from HTLV-1-infected T lymphocytes, Lkb1 heterozygosity can accelerate KrasG12D-induced pancratic ductal adenocarcinoma formation through the p53/p21 pathway., p21 and p27 were identified as the primary molecular targets of Arsenic trioxide against breast cancer., Data show that p21WAF1/Cip1 down-regulation was an independent prognostic factor by multivariate analysis., Findings indicate that p21 is a crucial downstream gene target and effector of GATA-1 during red blood cell terminal differentiation., HOXB13 is associated with an additive growth advantage of prostate cancer cells in the absence of or low androgen concentrations, by the regulation of p21-mediated E2F signaling., Reduction of levels of p21Cip1 and p16INK4a could be useful in development of treatments to induce transient cell division to increase corneal endothelial cell density., Results suggest that SAMD4B is a widely expressed gene involved in AP-1-, p53-and p21-mediated transcriptional signaling activity., p21WAF1/CIP1 may play a role in the inflammation regulation through PPAR transcription factors, strongly linked to lipid metabolism. It could also be involved in the control of the proliferation of monocytes/macrophages. Review., High CDKN1A is associated with uterine leiomyomas., Low expression of p21 may partially explain abnormal epithelial overgrowth in both oral verrucous hyperplasia and carcinoma., p21 may function to prevent atherogenesis by regulating the redox balance, which leads to the inhibition of adhesion molecule and chemokine expression in endothelial cells under laminar stress., Vestibular schwannomas that are merlin deficient exhibit loss of waf1 (p21)., increased levels of PBK/TOPK may contribute to tumor cell development and progression through suppression of p53 function and consequent reductions in the cell-cycle regulatory proteins such as p21., Hypermethylation does not contribute to Cip1 silencing in gastric cancer in a northern Brazil population., data suggest that MiTF mediates a survival signal linking Erk1/2 activation and p21 WAF1/CIP1 regulation via phosphorylation on serine 73, which facilitates cell cycle arrest, TXL upregulated the protein level of p21 and downregulated the protein levels of MMP-1 and MDR-1, Findings suggest that there is a significant association between the genetic polymorphism of p53, p21, and the risk of cervical cancer among Chinese southern women., p21 and p53 are recruited to ALT-associated PML-nuclear bodies after Nutlin-3a treatment, suggesting that they may play a previously unrecognized role in telomere maintenance, Low CIP1 expression is associated with neuroblastoma., p21 is a potential mediator of IFN-beta-induced attenuation of telomerase activity and tumor suppression, The cyclin-dependent kinase inhibitor p21WAF1/CIP1 is able to influence kinase activities both in a negative and positive manner., A total of 124 of 160 glioma samples displayed CpG island hypermethylation of both p73 and p21 genes associated with the loss of mRNA expression., Role of Hsp27 in cancer is not only for enhanced p53 proteolysis per se, rather it is also a critical determinant in p21 phosphorylation and translocation., These results suggest c-Myc could further repress p21 expression at the post-transcriptional level through some, but not all, members of miR-17 family., Data show that inhibition of ING2 expression accelerates progression of cells from G(1) to S-phase, and is accompanied by a decrease of p21 expression, and that regulation of p21 by ING2 is independent of p53., p21 over-expression was found to be associated with poor prognosis in esophageal squamous cell carcinoma., SPARC regulates, in a cell-autonomous manner, cell cycle progression and proliferation through the p53/p21(Cip1/Waf1) pathway., p21 deregulation is associated with the activation of stromal fibroblasts of oral cancers by a mechanism that involves the stimulation of SMA expression., The CDKN1A polymorphism at codon 31 is not a potential risk factor for development of Kaposi's sarcoma in subjects of either African or Caucasian ethnicity., p21, especially cytoplasmic phosphorylated p21, has an oncogenic role in promoting mammary tumorigenesis and metastasis., The expression of mRNA and protein of Cyclin A in hypertrophic scar changes from high level to low level as the hypertrophic scar develops, while the expression of P21cip1 changes from low level to high level., regulation of p16, p21, p27 and c-myc is increased by oridonin, which induces apoptosis and senescence in colorectal cancer cells, p21 plays a role in lung cancer drug-resistance process, Data show that DKK-1 knockdown PCa cells exhibited increased expression of the CDK inhibitor p21(CIP1/WAF1) and a 32% increase in G(1) arrest compared with control cells., Increased frequency of expression of P21 is associated with cirrhosis and hepatocellular carcinoma., Strategies to re-express epigenetically silenced p15(INK4b) and p21(WAF1) genes in acute myeloid leukemia., heterogeneous RB (pRb2 or p16) and p53 (p53, p14, or p21) pathway alterations occur frequently in Burkitt lymphoma, a new role for 14-3-3gamma in protecting p21 from MDMX-mediated proteasomal turnover, which may partially account for DNA damage-induced elevation of p21 levels independent of p53., We conclude that Ishikawa cells contain a subpopulation of cells with stem cell-like properties. Musashi-1 modulates endometrial carcinoma cell cycle progression and apoptosis via the stemness-related factors Notch-1, Hes-1 and p21(WAF1/CIP1), hSSB1 may positively modulate p21 to regulate cell cycle progression and DNA damage response, implicating hSSB1 as a novel, promising therapeutic target for cancers such as hepatocellular carcinoma, Recruitment of BRCA1 to the p53-binding region of the p21 promoter in response to DNA damage required methylation of Arg 754 of p300 by CARM1, These findings establish a novel MST3-NDR-p21 axis as an important regulator of G(1)/S progression of mammalian cells., Data show that ECRG4 interacts directly with ECRG1 to upregulate p21 protein expression, induce cell cycle G1 phase block and inhibit cancer cells proliferation in ESCC., Escape from p21-mediated oncogene-induced senescence leads to cell dedifferentiation and dependence on anti-apoptotic Bcl-xL and MCL1 proteins., Akt-mediated phosphorylation of p21 and protection of apoptosis are completely abolished by inhibitors of PI3K and Akt., Data show that VentX is a direct transcriptional activator of p53-p21 and p16ink4a-Rb tumor suppression pathways., the reduction of p21 protein levels plays an essential role in early-stage human papillomavirus-associated lung tumorigenesis and is correlated with poor relapse free survival, Hepatitis B virus X protein overcomes trans retinoic acid-induced cellular senescence by downregulating levels of p16 and p21 via DNA methylation., Erythromycin could restrain the proliferation of SH-SY5Y cells by downregulating c-myc and upregulating WAF1., Data successfully demonstrate the involvement of senescence gene p21 in the expression of stemness markers and osteogenic potential of mesenchymal stem cells., The cyclin-dependent kinase (Cdk) inhibitor p21(Cip1) adaptively binds to and inhibits the various Cdk-cyclin complexes that regulate eukaryotic cell division., Loss of p21 compromises the p53 transcriptional response in part due to p53 protein mislocalization and that ATM-inhibition gives rise to a similar mislocalization of p53 protein., these findings describe a novel mechanism whereby EZH2 activation during tumor progression represses p21, leading to suppression of cellular senescence and enhanced tumorigenicity., Induction of miR-93 expression and reduced p53 binding to p21 gene promoter account for loss of p21(sdi1) expression in senescent cells after DNA damage, suggesting a mechanism of in vivo carcinogenesis in aged tissue without repair arrest., This meta-analysis suggests that the p21 31Arg allele is a low-penetrant risk factor for cancer development, especially among whites., The results suggest a role for AP-1 in the proliferation, G(2)/M progression and inhibition of p21 expression in cervical cancer., phytoestrogens induce apoptotic cell death of ERalpha-negative breast cancer cells via p53-p21-dependent manner., P21 Ser31Arg polymorphism is not associated with cervical cancer., PI3 Kinase inhibition on TRAIL-induced apoptosis correlates with androgen-sensitivity and p21 expression in prostate cancer cells., The p21 31Arg/Arg genotype may serve as a potential marker for increased cancer risk., SNPs of p21 genes were not significantly associated with susceptibility to gastric cancer., SKIP is essential for p53 stress-induced expression of the p21, Data suggest that this novel role of caspase-2 as a translational regulator of p21 expression occurs not only independently of its enzymatic activity but also does not require known caspase-2-activating platforms., Expression of P21 showed no correlation associated with progression in B-CLL, Both sodium selenite and selenomethionine supplementations reduced ROS production, and p53 and p21 activation in MEHP-exposured prostate adenocarcinoma cells., The immunoexpression of p21waf1 was lower in the HPV-positive group compared to the HPV-negative group, although only the difference of p53 staining was statistically significant., Data show that in MCF7 cells, both ATM (p53, p21) and ATR (Chk1) pathways are defective leading to a complete lack of G2 arrest in response to bleomycin and ICRF-193., We conclude that low p21 and high survivin expression are poor prognosis indicators in FIGO stage I endometrial endometrioid adenocarcinoma, Eupatilin inhibits the growth of human endometrial cancer cells via G2/M phase cell cycle arrest through the upregulation of p21., activation of TP53 and its downstream effectors like CDKN1A by low concentrations of sagopilone is responsible for the relative apoptosis resistance of A549 cells, p21 regulates adhesion and microtubule dynamics in untransformed human mammary epithelial cells., Reports the identification of the microRNA miR-22 as a p53 target gene that selectively determines the induction of p53-dependent apoptosis by repressing p21., Tension force activates Ras-p38 MAPK pathways in periodontal ligament fibroblasts, which up-regulate p21 and arrest cell cycle progression at the G1 phase., The different LH subdomains, despite their sequence and thermodynamic differences, play similar roles in binding and inhibiting Cdk2/cyclin A., High p21 and low p53 expression in Inverted Papilloma suggests a non-p53-dependent regulation pathway., Gefitinib-induced p21 protein stability, rather than increased RNA accumulation, was responsible for the elevated p21 levels, study reports that UBCH8 and UBE2G1 and UBE2G2 cooperate with CRL4Cdt2 in promoting the polyubiquitylation and subsequent degradation of p21 and Cdt1, respectively, Stress granules component CUGBP1 was identified as a factor required for p21 mRNA stabilization., p27 expression seems to be more powerful than p21 expression in providing useful prognostic information in colorectal cancer, the ERK/ELK-1 cascade is involved in p53-independent induction of p21 and BAX gene expression., KLF4-siRNA inhibits PKCdelta-dependent p21(Cip1) promoter activity. PKCdelta increases KLF4 expression leading to enhanced KLF4 interaction with the GC-rich elements in the p21(Cip1) promoter to activate transcription, RNA-induced activation of p21/CIP1 gene expression inhibited the viability of hepatocellular carcinoma cells and clone formation., Data show that he senescence occurs in the manner dependent on p21., The results demonstrated that p21 has a critical role in the regulation of the activation of the FA-BRCA pathway and suggest a broader role for p21 in the orchestration of DNA repair following exposure to DNA crosslinking agents., HBx mutants with changes that correspond to a combination of core promoter mutations up-regulate SKP2, which then down-regulates p21 via ubiquitin-mediated proteasomal degradation, increasing hepatocellular carcinoma risk., Loss of p21 expression was frequently observed in lung cancers and malignant pleural mesotheliomas and aberrant methylation was one of the mechanisms of suppression of p21., N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) triggers MSH2 and Cdt2 protein-dependent degradation of the cell cycle and mismatch repair (MMR) inhibitor protein p21Waf1/Cip1., Suppression of Polo like kinase 1 (PLK1) by p21(Waf1) mediates the p53-dependent prevention of caspase-independent mitotic death., five types of traditional Chinese medicine can attenuate G1 growth arrest of HaCaT cells and dermal fibroblasts induced by UVB exposures, which was caused by down-regulating the expression of cell-cycle regulatory proteins p16, p21 and p53., turnover of p21 was independent of the SCF (skp2) E3 ligase but could be inhibited, at least in part, by reducing hdm2, although this depended on the cell type studied., Data suggest that in some systems p21(CIP) takes part in a mitosis control driving MYC-induced cellular growth into differentiation., lack of magnesium may increase p21(Cip1) and p27(Kip1) levels mediated by the decrease in ATP content and the activation of p53, resulting in the suppression of cell cycle progression from G1 to S phase in NRK-52E cells, Here, the authors report that human papillomavirus type 16 E6 targets the cellular factor p150(Sal2), which positively regulates p21(WAF1) transcription., 3'UTR inhibition and Cebpb mRNA compartmentalization were absent in primary fibroblasts, allowing Ras-induced C/EBPbeta activation and oncogene-induced senescence to proceed., 4-O-methylhonokiol causes p21-mediated human colon cancer cell growth inhibition through suppression of NF-kappaB., Results suggest that piroxicam/cisplatin combination might be tested in clinical settings in tumor specimens that express p21., Homozygous deletion of the FHIT gene, p21WAF1 protein expression and apoptosis in bilharzial bladder cancer., The present work shows that SEPW1 facilitates the G1 to S-phase transition by down-regulating expression of the cyclin-dependent kinase inhibitor p21., The p21 C31A, Ku80 A2790G, and MDM2 T309G genetic polymorphic variations are associated with the occurrence of head and neck cancer in the Saudi Arabia population., p21 prevents Puma and its downstream effector Bax from triggering the mitochondrial apoptotic pathway., p53-independent epigenetic repression of the p21(WAF1) gene in T-cell acute lymphoblastic leukemia., Transfection of siRNA specific for cMet, the HGF receptor, eliminated the HGF anti-proliferation effect on human bone marrow-derived stem cells and the HGF-mediated increase in p53, p21, and p27., Epstein-Barr virus Rta-mediated transactivation of p21 and 14-3-3sigma arrests cells at the G1/S transition by reducing cyclin E/CDK2 activity., Studied the regulation of cytoplasmic p21 through transfection of p21 siRNA, Akt2 shRNA and Akt2 constitutively active vector in the two cell lines; their effects on cisplatin-induced apoptosis were evaluated by flow cytometry., Describes the structure of a human p53 homotetramer encompassing both the DNA-binding and homo-oligomerization domains in complex with the natural p53-response element present upstream of the promoter of the CDKN1A (p21) gene., Our results suggest a role for variant p21 alt-a in hypoxia and for variant p21B in acute myocardial ischemia, Retinoid X receptor antagonist HX531 exerts anti-obesity/anti-diabetes properties by up-regulating the p53-p21 pathway, resulting in G0/G1 cell cycle arrest and the inhibition of cellular hypertrophy of adipocytes., results indicate that during the cellular response to low UVC fluences the ATR protein kinase up-regulates p21(WAF1/Cip1) and inhibits apoptosis, Zac1 is able to interact directly with the Sp1-responsive element in the p21(WAF1/Cip1) gene promoter., FIH activity is essential for tumor growth through the suppression of the p53-p21 axis, the major barrier that prevents cancer progression., based on our meta-analysis, p21 Ser31Arg polymorphism does not appear to act as an independent lung cancer risk factor, DP1, but not DP2, is uniquely involved in the regulation of the p53 and p21Waf1/Cip1 pathway, thereby augmenting senescence in human somatic cells., G1-arrest correlates with up-regulation of p21 in oral squamous cell carcinoma cell lines, Deficiency of p21 reduces Apaf-1 protein expression and inhibits caspase activation in curcumin-treated cancer cells., Functional blockade of the voltage-gated potassium channel Kv1.3 mediates reversion of T effector to central memory lymphocytes through SMAD3/p21cip1 signaling., Inhibition of Notch3 signalling induces rhabdomyosarcoma cell differentiation promoting p38 phosphorylation and p21(Cip1) expression and hampers tumour cell growth in vitro and in vivo., Although p21 expression was not correlated with survival incorporating p21 into a multivariable Cox model did contribute to improved model quality for predicting cancer-specific survival., Report induction of Fas-mediated extrinsic apoptosis, p21WAF1-related G2/M cell cycle arrest and ROS generation by costunolide in estrogen receptor-negative breast cancer cells., Widdrol breaks DNA directly in HT29 cells, resulting in checkpoint activation via Chk2-p53-Cdc25A-p21-MCM4 pathway and finally cells go to G1-phase cell cycle arrest and apoptosis., These results indicate both cooperative and interdependent roles for ARID3A and p53 in the transcriptional activation of p21(WAF1) in response to DNA damage., The subcellular localization of P21 may contribute to the development of hepatic cancer., DNA-PKCS negatively regulates p21 expression by directly interacting with the p21 transcription machinery via p53, driving the cell towards apoptosis., p53 and CDKN1A genotypes are associated with endometriosis, MEOX1 and MEOX2 activate p16(INK4a) in a DNA binding dependent manner, whereas they induce p21(CIP1/WAF1) in a DNA binding independent manner., NALM-6 cells, which have a higher expression of p21waf1/cip1 mRNA than other leukemia cell lines, were susceptible to spiruchostatin-B-induced cytotoxicity that resulted in induction of apoptosis., RNPC1 contributes to tumor resistance to radiotherapy, which likely occurs through a p21-mediated G/G accumulation mechanism, observations disclose PKCdelta as negative regulator of p21(Cip1/WAF1), which facilitates proliferation of insulin secreting cells under stress-free conditions, results indicate that STAT1 is implicated in the mediation of Ang II-induced HMC senescence through p53/ p21Cip1 pathway., This work indicates that Zac1 functions are regulated, at least in part, via non-covalent interactions with SUMO-1 for the induction of p21, which is important for the modulation of apoptosis., Suggest a novel apoptotic mechanism of genetically engineered adenovirus-mediated tumour-specific p53 overexpression through E1A-dependent p21 and MDM2 suppression., miR-663 modulates cell cycle and proliferation in nasopharyngeal carcinoma by regulating the expression of p21 cyclin-dependent kinase inhibitor., In hepatocellular carcinoma miR-519d is up-regulated by p53 and DNA hypomethylation and targets CDKN1A/p21, PTEN, AKT3 and TIMP2., these data collectively indicate that beta1-integrin-related cell death is closely associated with EMT phenotypes and activation of the p53-p21 pathway is partly involved in the acquisition of resistance to apoptosis induced by beta1-integrin silencing., LCoR recruitment by KLF6 regulates expression of the cyclin-dependent kinase inhibitor CDKN1A gene., Raf-1/JNK /p53/p21 pathway may be involved in apoptosis, and NFkappaB1 may play a possible role in inhibiting apoptosis., Genetic variations in the cell cycle genes encoding p53 and p21 are associated with idiopathic pulmonary fibrosis disease development and progression., FoxM1, p27(kip1) and p21(waf1/cip1) showed distinct immunoreactivity according to histological subtype, which may help in the differential diagnosis of pulmonary neuroendocrine tumours., the balance between cancer cell death and arrest after p21 up-regulation depends on the specific effects of p21-induced ROS on the mitochondria., p21 (rs733590) C/T SNP was not found to be associated with breast cancer pathogenesis. However, we found that a reverse mutation T/C may be associated with breast cancer occurrence., In human breast epithelial cells, androgen receptor signaling requires p21 for MAPK activation., demonstrated that while TFAP2C and Myc can downregulate the CDKN1A promoter independently, KDM5B acts as a corepressor dependent on the other two proteins, IGFBP-rP1-induced growth arrest is associated with enhanced expression of the cyclin-dependent kinase inhibitor p21., The BRCA1/Chk1/p53 pathway mediated the upregulation of p21(Cip1/Waf1). We also demonstrated that the NO-mediated up-regulation of p21(Cip1/Waf1) was inversely correlated with the activation status of the p38MAPK pathway., SFN increases p21(Cip1) promoter transcription via a mechanism that involves SFN-dependent stabilization of p53 and increased p53 and Sp1 binding to their respective response elements in the p21(Cip1) promoter, This report describes how carboxylated multiwalled carbon nanotubes (MWCNTs) induce p53-independent p21 expression and cell cycle arrest., Genetic polymorphisms in CDKN1A gene is associated with autoimmune disease., The results suggest that p27 T109G polymorphism individually or in combination with p21 (C98A and C70T) polymorphisms increases risk of SPM in patients with index SCCHN., Data indicate that in arecoline treated oral squamous cell carcinoma cells, elevated levels of p21 and p27 could be downregulated through the reactive oxygen species/mTOR complex 1 (ROS/mTORC1) pathway., the role of TAK1 in cell death, cell cycle regulation and apoptosis after X irradiation is independent of NF-kappaB, p38 MAPK, and ERK phosphorylation, and dependent, in part, on p21 induction, survivin may act as a transcription factor or cofactor to interact with p53 on the p21(WAF1/CIP1) promoter leading to the inhibition of p21(WAF1/CIP1) expression at least in part by neutralizing p53-mediated transcriptional activation of the p21 gene., Attenuated p21 expression may render some p53 wild type tumors sensitive to a combination of DNA damage plus checkpoint inhibition., Data show that the hESC-enriched miRNA family miR-302 (miR-302a, miR-302b, miR-302c, and miR-302d) directly contributes to regulation of p21 expression in hESCs and, thus, demonstrate a novel function for miR-302s in hESCS., TLP mediates p53-governed transcriptional activation of the p21 upstream promoter., These results thus implicate the E2A-CDKN1A transcriptional axis in the control of megakaryopoiesis and reveal the lineage-selective inhibition of this axis as a likely mechanistic basis for the inhibitory effects of cAMP signaling., ETS1, ERK2 andMxi2 are important complex partners initiating increased p16INK4a and p21waf1/cip1 activation in renal tumor cells, Ccr4d functions as an anti-proliferating protein through the induction of cell cycle arrest via a p21-dependent and p53-independent pathway and suggest that Ccr4d might have an important role in carcinogenesis., miR-519 promotes DNA damage, alters Ca(2+) homeostasis, and enhances energy production; together, these processes elevate the expression level of p21, promoting growth inhibition and cell survival., Positively stained p53, p21, and prelamin A proteins are upregulated in senescent aortic smooth muscle cells of a nephrectomixed rat model., we present here data suggesting that p21 and hif1alpha mRNA plasma expressions may be used as markers for complicated pregnancies, We identified three new CRC risk loci at 6p21 (rs1321311, near CDKN1A; P = 1.14 x 10(-10)), 11q13.4 (rs3824999, intronic to POLD3; P = 3.65 x 10(-10)) and Xp22.2 (rs5934683, near SHROOM2; P = 7.30 x 10(-10))., Study suggests overexpression of BMPRIB may arrest and induce the differentiation of glioblastoma cells due to upregulation of p21 and p27kip1 and that decreased expression of BMPRIB in glioblastoma cells contributes to glioma tumorigenicity., p21 activity as inhibitor of cell cycle progression would be mediated not only by the inhibition of CDKs but also by the transcriptional down-regulation of key genes., The activation of p21(Waf1/Cip1) was significantly up-regulated over time, but there was no change in the level of CDK2 expression by treatment of HEK293 cells with various concentrations of veterinary antibiotics., Findings implicate blockade of the ATM-p53-p21 pathway at the level of p21 as a unrecognized determinant of early disease recurrence following successful cytoreduction., In response to replicative stress and unresolved DNA damage, p53 is hyperactivated in FA cells and triggers a late p21(Cdkn1a)-dependent G0/G1 cell-cycle arrest., results suggest downregulation of p21waf1/cip1, which is a characteristic feature of NALM-6/SP-B cells, was important for their resistance to spiruchostatin B (SP-B)and this SP-B resistance could be overcome by the introduction of exogenous p21waf1/cip1, Data show that regulation of p21 by ID1 and ID3 is a central mechanism preventing the accumulation of excess DNA damage and subsequent functional exhaustion of cancer-initiating cells (C-ICs)., Binding of ZONAB to mRNA is activated by GEF-H1 via Rho stimulation and also mediates Ras-induced p21 expression., The activation of p21 transcription required an intact PCAF HAT domain., Trim71 cooperates with microRNAs to repress Cdkn1a expression and promote embryonic stem cell proliferation, p21CIP1 regulates metastasis by mediating reciprocal switching between invasion and proliferation, These findings provide biological insights into the possible role of nonsense-mediated mRNA decay in diverse biological pathways mediated by CDKN1A., results indicate that the angiostatic action of IL-12-stimulated lymphomononuclear cells may lie in the capability to arrest endothelial cells in G1 phase through a mechanisms mainly based on the specific up-regulation of p21(Cip1/Waf1), the overexpression of p21 Waf1/Cip1 was involved in inhibition of proliferation and DNA synthesis in colon adenocarcinoma HT-29 cells, Cyclin D1 was down-regulated, while p21 expression was up-regulated by EGCG in dose- and time-dependent manners., Together, these results suggest that the p53-p21 pathway is required for efficient herpes simplex virus type 2 lytic replication cycle., P12(CDK2-AP1) was found to be significantly downregulated in 60 breast cancer tissues compared to corresponding non-tumorous tissues., findings elucidate a NUPR1-PI-3-K/Akt-phospho-p21 axis that functions in p53-negative, inflammatory breast cancer cells to enhance chemoresistance, Low concentration of dihydrotestosterone induced lower mRNA levels in the p53 and p21 genes in non-transformed epithelial prostatic cells. High dihydrotestosterone concentrations induced a significant increase in the expression of the p53 and p21 genes., Data indicate LNP-dsP21-322-2'F facilitates tumor suppressor p21(WAF1/CIP1) activation in vivo leading to regression/disappearance of tumors., data suggest that EZH2 is overexpressed in B-ALL and promotes the progression of B-ALL by directly mediating the inactivation of tumor suppressor genes p21 and PTEN, Results highlight the potential roles of ERalpha and p21(WAF1) in growth inhibition of cancer cells mediated by proteasome inhibitors, such as bortezomib., Co-culture of CB CD34(+) cells with mesenchymal stromal cells, especially in the absence of cytokines, maintained mRNA expression of p21 and p57 genes in ex vivo expanded CD34(+) cells., A structural adaptation mechanism involving a stretchable dynamic linker helix allows p21 to promiscuously recognize the various Cdk (cyclin-dependent kinase)-cyclin complexes that regulate cell division., Immunohistochemical determination of p21 may be helpful for the typing of ovarian tumors as benign, borderline and malignant or serous and mucinous., these results highlight an important role for p21 and p/CAF in promoting breast cancer cell migration and invasion at the transcriptional level and may open new avenues for breast cancer therapy., [review] Small molecules like p21 and PUMA may play a role in the pathogenesis of rheumatoid arthritis., the HIC-5- and KLF4-dependent mechanism transactivates p21(Cip1) in response to anchorage loss, Tyrosine phosphorylation of the p21 cyclin-dependent kinase inhibitor facilitates the development of proneural glioma, Exposure of cells to aldosterone for 3 or 5 days increased senescence-associated beta-galactosidase staining, p21 and TNF-alpha mRNA expression., Cip1 polymorphisms are associated with hepatocellular cancer., Low doses of parthenolide inhibit tumor promotion and epigenetically modulate p21 expression, highlighting the potential role of this drug as a chemopreventive agent and in epigenetic cancer therapy., Search of the ENCODE database identified the Sp1/Sp3 palindrome element as the only vertebrate-conserved element within the 500-bp proximal p21 promoter region, indicating its fundamental importance., GSK3beta phosphorylation of the KLF6 tumor suppressor promotes its transactivation of p21., The data indicated a novel role for Wig1 in RNA-induced silencing complex target accessibility, which is a key step in RNA-mediated gene silencing. Fine tuning of p21 levels by Wig1 was essential for the prevention of cellular senescence., findings substantiate PIR2/Rnf144b as a potentially critical component of epithelial homeostasis, acting downstream of DeltaNp63alpha to regulate cellular levels of p21(WAF1/CIP1) and DeltaNp63alpha, Gatifloxacin induces S and G2-phase cell cycle arrest in pancreatic cancer cells via p21/p27/p53, age-dependent p400 downregulation and loss of H2A.Z localisation may contribute to the onset of replicative senescence through a sustained high rate of p21 transcription, Murine double minute 2 (MDM2) protein levels were decreased in AD cells relative to control lymphoblasts, suggesting an impairment of FOXO3a degradation., The expressions of p21(Cip1/WAF1), Gadd45alpha and p53 are associated with the clinicopathologic features and prognosis in breast cancer., Androgen receptor down-regulates basal p21 expression through the PIRH2-p53-p21 axis in androgen- independent prostate cancer cells, thereby priming the cells to UV-induced apoptosis., Galectin-3 regulates p21 protein stability in human prostate cancer cells., In the present study, the p21 codon ser31arg polymorphism was significantly associated with increased risk for acute myeloid leukemia., our results strongly suggest that p21CIP1 acts as an effector of cytoplasmic gelsolin and plays an important role in gelsolin-induced monocytic differentiation of U937 cells., HIC1 is a direct transcriptional repressor of p21., Data indicate that the signal transducer and activator of transcription 6 (Stat6) as an important cell differentiation regulatory protein functioning by interacting with Sp1 to activate the p21 and p27 gene promoters in breast cancer cells., p53 can repress transcription of cell cycle genes through a p21(WAF1/CIP1)-dependent switch from MMB to DREAM protein complex binding at CHR promoter elements., Consistent with p53 derepression, NF90/NF45-depleted HeLa cells displayed elevated poly ADP-ribose polymerase (PARP) cleavage and susceptibility to camptothecin-induced apoptosis., p21(C31A)polymorphism contributes to the risk of primary open-angle glaucoma onset in Russian and Buryat populations, these results suggest that the loss of p21 results in an aberrant increase in the mitochondrial mass and in mitochondrial dysfunction in HCT116 cells, indicating that p21 is required to maintain proper mitochondrial mass and respiratory function., TRIM39 has a role in regulating cell cycle progression and the balance between cytostasis and apoptosis after DNA damage via stabilizing p21, The p21(WAF1/CIP1) gene may have been methylated and hence is inactive in MCF-7/ADR cells., CD34(+) cells from patients with lower-risk myelodysplastic syndrome present p21 dependent premature senescence., Waf1 is expressed during the follicular phase in the submucosal layer of the myometrium., The three p21 SNPs (rs1801270, rs3176352, and rs1059234) was in linkage disequilibrium., during cytomegalovirus infection, pUL29/28 and pUL38 contributed to inhibition of p21CIP1 and caspase 1 expression; expression of pUL29/28 and pUL38 contributed to an increase in steady-state levels of p53; study identified 2 additional HCMV proteins, pUL29/28 and pUL38, which participate in regulation of p53 transcription activity, The p21 acetylation at sites 161 and 163 is required for stabilization of functional p21 after DNA-damaging stress., Two separate defects in p53 signaling appeared common, The p21 overexpression leads to a dual outcome, activating the G/S arrest of the cell cycle or the apoptotic pathway through mitochondria, depending on its intracellular levels., Oleuropein down-regulates NF-kappa B and cyclin D1 but activates p21 in MCF-7., Interleukin-20 promotes migration of bladder cancer cells through extracellular signal-regulated kinase (ERK)-mediated MMP-9 protein expression leading to nuclear factor (NF-kappaB) activation by inducing the up-regulation of p21(WAF1) protein expression, The negative expression of p21 correlates with disease survival and may be a poor prognostic factor in patients with resected gastric cancer treated with adjuvant chemotherapy., The p21 C70T polymorphism is associated with decreased risk of prostate cancer in Slovak men., Data show that E2F1 overexpression, due to p53 or p21 inactivation, promotes expression of human oncoprotein CIP2A., one of the two single nucleotide polymorphisms of CDKN1A seems in some way related to Alzheimer's disease, Data indicate TRIM3 and p21 interact in cells., Up-regulation of p21 protein is expected to play a significant role in congenital cholesteatoma, Data indicate BOZF1 represses transcription of CDKN1A by inhibition of p53 acetylation and Sp1 binding., Fndings indicate that miR-17-5p/20a promote gastric cancer cell proliferation and inhibit cell apoptosis via post-transcriptional modulation of p21 and TP53INP1., Data show that histone deacetylase inhibitors (HDACi) induce p21 transcription and reduce cell proliferation of MDA-MB231, an ERalpha-negative mammary tumor cell line, in a H2A.Z dependent manner., Results demonstrate that both TRB3 and p21(Cip1) are critical molecules in the homocysteine signaling cascade., Our data suggest that inactivation of p53 and p21 may play an important role in the evolution of carcinoma ex pleomorphic adenoma, FMN2 enhances expression of the cell-cycle inhibitor p21 by preventing its degradation, The data collectively suggest that triiodothyronine and its receptor signaling suppresses cell proliferation by upregulating endoglin, in turn, affecting p21 stability., TP53, P21 and P27 positivity correlates with survival outcome in low-stage epithelial ovarian cancer., HSF1/SESN3/reactive oxygen species/p21(Cip1/WAF1)-mediated deceleration of cell growth may contribute to cell defense systems protecting the organism from excessive proliferation of cells that overexpress activated Ras oncoproteins., MiR-224 is overexpressed in inflammatory bowel disease cancers and targets p21, a key cell cycle regulator., p53 promotes VEGF expression and angiogenesis in the absence of an intact p21-Rb pathway., human myeloid cell line constitutively overexpressing EVI1 was partially resistant to etoposide and daunorubicin, Based on our observation of G1/G0 cell cycle arrest in Batten cells, we monitored p21 expression, which was higher in Batten disease cells than in normal cells., Data indicate that exposure to benzylguanine (6BG)/temozolomide (TMZ) led to increases in p53, p21, gamma-H2AX, and mitochondrial DNA damage., Enhanced the association of PPARgamma with the p21(WAF1/Cip1) promoter., FXR1P muscle-specific isoforms bind p21 mRNA via direct interaction with a conserved G-quadruplex located in its 3' untranslated region. The FXR1P/G-quadruplex complex reduces the half-life of p21 mRNA., HCV core protein suppresses p21(Waf1/Cip1) gene expression through miR-345 targeting., The results indicated that miR-22 directly targets CDKN1A, and the expression of miR-22 was inversely correlated with CDKN1A expression in hepatitis B virus-related hepatocellular carcinoma, Suggest that HBx induces hepatocarcinogenesis via PKCalpha-mediated overexpression of cytoplasmic p21 and IFN-beta suppressed these molecular events by shifting p21 to the nucleus., miR-223 functions as a tumor suppresser in osteosarcoma and miR-223/Ect2/p21 signaling is an important pathway that regulates the osteosarcoma cell cycle progression and proliferaion, EZH2 has a role in regulation of p21 and mutant p53 involved in growth of ovarian cancer, Surprisingly, we found that GRP/GRP-R differentially induced expressions of p21 and p27. Silencing GRP/GRP-R decreased p21, but it increased p27 expressions in neuroblastoma cells., In large airway epithelium of smokers with and without COPD, the cytoplasmic p21 inhibits cell apoptosis, promotes cell proliferation and correlates with squamous cell metaplasia thus representing a potential pre-oncogenic hallmark, OSU-03012 induces apoptosis in human esophageal carcinoma cells through a p53/Bax/cytochrome c/caspase-9-dependent pathway., EVI1 binds to DeltaNp63 promoter element directly and down regulates its expression, inducing the expression of p21 in colon carcinoma cells that do not express p53, that eventually delay cell cycle progression at G0/G1 phase., Report prostate cancer G0/G1 cell cycle arrest via cdk4/p21 pathway., in 85 sporadic parathyroid adenomas, study identified alterations in 5 adenomas, Transcription of the p21Waf1/Cip1 and JNK-1 genes is affected by inhibition of the early growth response-1(Egr-1)., CDK7 involved in phosphorylation/activation of CDK4 and CDK6; existence of CDK4-activating kinase(s) other than CDK7; and novel CDK7-dependent positive feedbacks mediated by p21 phosphorylation by CDK4 and CDK2 to sustain CDK4 activation., Data suggest that CDKN1A stability in keratinocytes is regulated (up-regulation; down-regulation) by mechanisms involving S100A11 (S100 calcium binding protein A11) and ubiquitin-independent proteasomal degradation., Immunostaining of p16(INK4a) and p21(WAF1/Cip1) provides additional information on the cytological diagnosis of squamous intraepithelial lesions of the uterine cervix., An unexpected role of p38 in cell cycle regulation in response to Aurora B inhibition, by promoting the transcriptional elongation of the cell cycle inhibitor p21., miR-17-5p is induced in irradiated OC3 cells and it downregulates p21 protein expression, contributing to the radioresistance of OC3 cells., Thus, our findings highlight the cyclin D1/p21 signaling axis as a critical regulator of TGFb-mediated tumor growth initiation and local tumor cell invasion, both in vitro and in vivo., Data indicate that p27 expression and microvessel density (MVD) dramatically decreased during the transition from in situ to invasive ductal carcinomas (IDC), and a low c-kit expression was indicative of IDC relapse., ATR stabilizes the CDKN1A message in response to UV damage through Cdk1-related cytoplasmic accumulation of HuR., Data indicate there was no statistical significance observed between the immunoexpression of p16, p21, p27, and pRb with nodal metastasis, depth of invasion, and presence of vascular or perineural invasion., Studies indicate there is no association between p21 Ser31Arg polymorphism and cervical cancer risk in Asians., FMN2 is a crucial protein involved in the control of p21., CD44 increases phorbol ester-induced expression of p21WAF1 by stabilizing its mRNA and extending protein half-life, Phosphorylation by Lats2 induces degradation of p21 and promotes apoptosis. Lats2 overexpression induces p21 degradation, activation of caspase-3 and caspase-9, and apoptosis., The present report shows that p16 positively regulates the basal expression of p21 in various human cell types and mouse embryonic fibroblasts., Our data suggest the possibility of epigenetic modification of Prostate-derived Ets factor due to DNA methylation and involvement of the cell cycle inhibitor p21., Ex vivo expansion protocols involving hypoxic preconditioning inhibit cell senescence in endothelial progenitor cells by hypoxia-induced hypoxia-inducible factor-1alpha-TWIST-p21 axis., Senescence caused by AP4-deficiency was prevented by depletion of p16 and/or p21, demonstrating that these factors mediate senescence caused by AP4 loss., Cyclin-dependent kinase inhibitors, p21 and p27, are upregulated by PXD101 in a sustained fashion in histone deacetylase inhibitor resistant cell lines., A significant 2.21-fold increase in the chance of developing breast cancer was observed in the candidates carrying at least one allele Arg mutant in p21/CIP1 genotype., Treatment with metformin upregulated the expression of p21CIP and p27KIP, but downregulated cyclin D1 levels, both in vitro and in vivo, Knockdown of p21 partially rescues the cell growth arrest induced by the BCA2 siRNA., The minor alleles of polymorphisms in CDKN1A (p21) gene may act as risk factors for the development of RB., These observations suggest an intrinsic cooperation between p21 and p27 CKIs in the activation of stress-induced cellular senescence and tumor progression in glandular proliferative lesions, Downregulation of mutant p53 with concomitant enhanced expression of p21(waf1/cip1) and its transcriptional trans-activators may contribute toward EZH2-mediated suppression of pancreatic ductal adenocarcinoma., Cigarette smoke extracts (CSE) increased the expression of p21 in CSE stimulated bronchial epithelial cells and carbocysteine was able to reduce this effect., p21-mediated RNR2 repression restricts HIV-1 replication in macrophages by inhibiting dNTP biosynthesis pathway., p21 is required for sustained liver regeneration and tumour development in chronic liver injury. p21 is a negative prognostic marker in human hepatocellular carcinoma., E2F4 complexes are effectors of p21-dependent p53-mediated repression., The genes c-Myc, p21, and p16 were correlated with the prognosis of triple-negative breast cancer, These observations suggest that RAGE promotes premature senescence of proximal tubular epithelial cells by activation of endoplasmic reticulum stress-dependent p21 signaling., Dosage of Dyrk1a repositions cells within a p21-CycD1 signaling map, directing each cell to either proliferate or to follow two distinct cell cycle exit pathways characterized by high or low CycD1 and p21 levels., P21 expression correlates with the 5 year survival rate in esophageal squamous cell carcinoma patients., Nuclear and cytoplasmic p21 protein levels were significantly reduced and increased in gastric cancer lesions, respectively. Low nuclear p21 or high cytoplasmic p21 correlated with shorter overall survival and clinicopathologic characteristics., Wnt/beta-catenin signaling mediates the senescence of bone marrow-mesenchymal stem cells from systemic lupus erythematosus patients through the p53/p21 pathway., p21 gene promoter contains numerous p53 target sequences, some of which have inverted repeats capable of forming cruciform structures., p53/p21 Pathway involved in mediating cellular senescence of bone marrow-derived mesenchymal stem cells from systemic lupus erythematosus patients., upregulation of HOTAIR contributes to the cisplatin resistance of lung adenocarcinoma cells, at least in part, through the regulation of p21 expression., our data demonstrate that CtIP is required for DNA damage-induced P21 induction., Intestinal cell proliferation and senescence are regulated by receptor guanylyl cyclase C and p21., Our results suggest p21 expression may serve as a new biomarker to predict clinical outcome in patients with myelodysplastic syndrome, Our findings thus indicate that TSG101 regulation of p21 is an important factor in the cellular function of TSG101., Data suggest that assessing expression of thymidylate synthase and in conjunction with p21(WAF1)/p53 of colon cancers may improve the selection of patients suitable for 5-fluorouracil (5FU)-based adjuvant chemotherapy., Data indicate that p21 forms a complex with ZEB1 at the miR-183-96-182 cluster promoter to inhibit transcriptional repression of this cluster by ZEB1, suggesting a reciprocal feedback loop., Data suggest that ESR1 (estrogen receptor 1) regulates cell cycle by suppressing expression of p53/p21 (tumor protein p53/cyclin-dependent kinase inhibitor 1A protein) and up-regulating proliferating cell nuclear antigen (PCNA)., Airborne particulate matter exposure induced cytoplasmic p21(CIP1/WAF1) retention, ERK1/2 activation, cytoskeleton remodeling and the acquisition of a senescence-like phenotype in lung cells., these data demonstrate that p21 is important for a fine-tuned control of the Cdk1 activity in mitosis, and its proper function facilitates a smooth mitotic progression., Immunofluorescence expression (IFE) of cell cycle regulators p16ink4a, p21, p27, in association with Ki-67, p53 in cell cultures, obtained from different types of cervical intra-epithelial lesions, was assessed., Rbm24 is a novel player in the p53 pathway, which may be explored to restore proper cell cycle control in p53-deficient tumors via p21., The same result was achieved by knocking down p53 and p21 with siRNA in p53-wt cells, indicating that p53 and p21 play a crucial role in MHY336-induced cell cycle arrest and apoptosis, The p53-CDKN1A-Bax signaling pathway appears to be activated in recurrenct spontaneous abortion., Shikonin induces cell cycle arrest in human gastric cancer by Egr1-mediated p21 gene expression., A pivotal role of arginine 213 determines the p53 mediated functions of p21 in human cancer cells., Existence of a tri-allelic polymorphism in the promoter of p21(Waf1/Cip1). It has also shown the heterozygous genotype 9T/11T to be a potential risk factor for gastric cancer in the Chinese population.[meta-analysis], Association of p21 with NF-YA suppresses the expression of PLK1 and prevents mitotic death in response to DNA damage., TDE2 may have an effect on tumor cell growth by influencing the expression of SREBP and p21., p21 transcription during replicative senescence of HEFs is up-regulated by increase in DNA binding activity and interaction between p53 and Sp1 via phosphorylation., the significant association of p21 mutation and hypermethylation leads to the complete inactivation of p21 gene in Indian female breast cancer patients., Resveratrol caused apoptosis in cigarette smoke-induced cancer cells by reduction of long patch base excision repair activity and this phenomenon largely depends on p21., G9a functions as a coactivator for p21 transcription, and directs cells to undergo apoptosis., hTOP3alpha interacts with p53, regulates p53 and p21 expression, and contributes to the p53-mediated tumor suppression, upregulation of p53 and p21 via HO-1 induction and subsequent release of iron with accumulation of H-ferritin may confer resistance to oxidative damage in cancer cells frequently challenged by redox-cycling anticancer drugs., Data suggest that EZH2 depletion promotes the progression of senescence by mediating the activation of tumor suppressor genes p21 and p16., Impact of Dux4 on p53/p21 signal pathway, which controls the checkpoint in cell cycle progression. Overexpression of Dux4 increased p21 mRNA and protein level, while expression of p53, phospho-p53 remained unchanged., results suggest that activation of the p21 upstream promoter is mediated by interaction between specific regions of TLP and p53, PKCdelta activates a MEKK1/MEK3/p38delta MAPK cascade to increase p53 levels and p53 drives p21(Cip1) gene expression., High CIP1 expression is associated with vascular invasion in gastric cancer., CDKN1A variant rs762623 is associated with the development but not the propagation of progressive liver disease in non-alcohol-related fatty liver disease., Knockdown of NS inhibited proliferation, arrested the cell cycle, and induced apoptosis through p53 and p21(Waf1/Cip1) pathways in MOLT-4 cells., the meta-analysis suggested that, in the p21 Ser31Arg polymorphism, Ser-allele and Ser/Ser genotype might be risk factors for gastrointestinal tract tumor in Asian populations, The loss of expression of Stat1 and p21 proteins corresponded to lymph node metastasis, advanced stage, tumor dedifferentiation, and poor prognosis in patients with pancreatic cancer., Our findings suggest that the 3'UTR P21 polymorphism may play an important role in the pathogenesis and initiation, but not in the progression, of undifferentiated nasopharyngeal carcinoma, while interaction with PCNA was important for targeting p21 to the CRL4Cdt2 ligase re-localized to MVM replication centers, bone marrow mesenchymal stromal cells affect the cell cycle arrest effect of genotoxic agents on acute lymphocytic leukemia cells via p21 down-regulation., We show for the first time the presence of HER2/HER3 heterodimers and the loss of p21 expression in HER2+ breast cancer predicts a significantly poorer outcome when submitted to adjuvant trastuzumab, These show high p21 and CD166 expression at the pretreatment biopsy were associated with tumor regression and poor prognosis in patients treated with 5-FU based chemoradiotherapy, Following upregulation, PRP19 repressed cell proliferation and tumor growth by upregulating the expression of the cell cycle arrest protein p21 in lung carcinoma tissues., we provide genetic and biochemical evidence that the JMJD5/CDKN1A (p21) axis is essential to maintaining the short G1 phase which is critical for pluripotency in human embryonic stem cells, The assessment of p53 and p21 can be expensive, but it proves to be a useful tool in difficult cases, this study highlights a novel SATB1-p21 axis that plays an important role in the disease progression of cutaneous CD30+LPDs, which provides novel molecular insights into this disease and possibly leads to new therapies in the future., APTR associates with the promoter of CDKN1A/p21 and this association requires a complementary-Alu sequence encoded in APTR. A different module of APTR associates with and recruits the Polycomb repressive complex 2 (PRC2) to repress the p21 promote, Suppression of p21Rac activity assists innate immunity in bactericidal activity and may induce remission in inflammatory bowel disease., Atherosclerotic plaque smooth muscle cell proliferation is reduced via a p21-dependent mechanism., Whole-genome sequencing of bladder cancers reveals somatic CDKN1A mutations and clinicopathological associations with mutation burden., provide evidence that p21 is activated in aneuploid cells by reactive oxygen species (ROS) and p38 MAPK, P53 and p21 null cells escaped complete arrest., Notch1-mediated repression of p21(waf1/Cip1) expression results in the inhibition of cell death and keratinocytes transformation., p21 rs3176352 G>C and p73 rs1801173 C>T SNPs are associated with increased risk of esophageal squamous cell carcinoma, PLZF can directly repress transcription of CDKN1A encoding p21, PLZF-RARalpha as an oncogenic transcriptional repressor of cyclin-dependent kinase inhibitor 1A (p21WAF/CDKN1A) and tumor protein p53 (TP53) genes, Our findings highlight a PFTK1-CCNY complex in activating noncanonical Wnt signaling in HCC cells., p57 and p21 serve nonredundant functions in trophoblast giant cells; the role of p21 in suppressing apoptosis is restricted to terminally differentiated cells., Low Cip1 expression is associated with ovarian cancer., We demonstrated that HDAC4 promotes gastric cancer cell progression mediated through the repression of p21., Findings shed novel light on the roles of miR-224/p21(WAF1/CIP1) signalling in the DDP resistance of LA cells, and targeting it will be a potential strategic approach for reversing the DDP resistance in human LAs., Expression of p21 gene decreased in endometrial cancer., the results suggest Cables1 as a novel p21 regulator through maintaining p21 stability and support the model that the tumor-suppressive function of Cables1 occurs at least in part through enhancing the tumor-suppressive activity of p21., p53, KLF4, and p21 showed altered expression patterns in pulmonary neuroendocrine neoplasms. Lack of KLF4 and p21 expression was associated with accumulation of aggressive features in typical carcinoids., SET/TAF-Ibeta inhibits FoxO1 acetylation and activates its transcriptional activity toward p21, miR-17 promotes the tumor growth of synovial sarcomas by post-transcriptional suppression of p21., Data showed that BRG1 as target protein of UCA1 with anti-oncogenic features in bladder cancer cells. UCA1 blocked recruitment of BRG1 to its target promoter, and thus led to reduced expression of p21 and accelerated cell growth., results establish that inactivation of p21 leads to increased apoptosis upon telomerase inhibition and thus identify a genetic vulnerability that can be exploited to treat many human cancers containing either wild-type or mutant p53., HMGB1 deficiency-induced inhibition of cell proliferation was mediated by p21, which was induced via a Sp1-dependent mechanism. Data demonstrate a novel oncogenic role of HMGB1 in promoting human melanoma cell proliferation., An increase of cytoplasmic nuclear p21 and activated caspase-3 expression., Data have identified a novel TWIST2-p21 axis that regulates the cell cycle of both normal and leukemic hematopoietic cells, which implicates TWIST2 as a novel tumor suppressor in human acute myeloid leukemia., In conclusion, p53, p21 and Cdc2 may be involved in the occurrence, development and recurrence of laryngeal squamous cell carcinoma., Our study demonstrated that EBNA3C significantly induces Pim-1 mediated proteosomal degradation of p21, conclude that p21/cyclin E pathway is crucial in modulating the anticlastogenic function of Bmi-1, Functional studies reveal that p21 and p53 cooperate to facilitate Mdm2-dependent Slug degradation and that this p53 function is mimicked by p53(R273H), a mutant lacking trans-activating activity., no association between rs1059234 polymorphism of p21 gene and risk of endometrial cancer, SAHA/bortezomib up-regulated the expression of CDKN2A and CDKN1A but did not affect the level of BCL2L11 or BHRF1 (viral homologue of BCL2)., FAL1 associates with the epigenetic repressor BMI1 and regulates its stability in order to modulate the transcription of a number of genes including CDKN1A., The proliferation inhibition and apoptosis of EC9706 cells mediated by SIRT3 downregulation may be closely associated with the expression levels of p21, Bcl-2 and Bax proteins., OXR1 upregulates the expression of antioxidant genes via the p21 signaling pathway to suppress hydrogen peroxide-induced oxidative stress and maintain mtDNA integrity., osteoclastogenic activity of translationally-controlled tumor protein (TCTP) with reciprocal repression of p21, The CDKN1A (rs1801270) mutant genotype was associated with decreased risk of hematologic toxicity in gastric cancer patients., Two states--quiescence and cell cycling--can coexist within an isogenic population of human cells and resulted from low basal expression levels of p21., Epstein-Barr virus nuclear antigen 3A promotes cellular proliferation by repression of the cyclin-dependent kinase inhibitor p21WAF1/CIP1, FOXA1/2 is required for p53-independent p21 expression, KAISO is a regulator of p53-mediated transcription of CDKN1A and apoptotic genes, There is an ER stress-dependent p53 pathway that suppresses p21 and lowers the apoptotic threshold to genotoxic drugs. This prevents p21 from promoting COP1-mediated 14-3-3sigma degradation and leads to G2 arrest., The time-course of decreasing ROS coincides with an increase in cell number and decreasing p21 protein levels, indicating a release from radiation-induced growth arrest., LKB1 mediates CDKN1A degradation in response to ultraviolet DNA damage., Cigarette smoking and overexpression of p53 or p21 are associated with poor prognosis in non-small cell lung cancer., Results propose that combined TP53/CDKN1A mutation with loss of function of both proteins defines a molecular subset of bladder cancer with particular sensitivity to the combination of a DNA-damaging chemotherapy as gemcitabine and a Chk1 inhibitor., Underexpression of Cip1 is associated with melanoma., Downregulated p21 expression., Chidamide treatment significantly decreased the expression of p21 and increased the ratio of Bax/Bcl-2 expression., Knockdown of endogenous Msi1 protein inhibited the growth and tumor formation by activating the cell cycle suppressor p21cip, PKCeta promotes senescence through its ability to upregulate the expression of the cell cycle inhibitors p21Cip1 and p27Kip1 and enhance transcription and secretion of IL-6., The increase in p21 expression in RPE cells not only inhibits the proliferation and migration of RPE cells in vitro, but also suppresses the development of proliferative vitreoretinopathy in vivo., Analysis of breast cancer samples reveals that a high LRH-1 level is inversely correlated with CDKN1A expression in breast cancer patients and is associated with poor prognosis, up-regulation of p21(WAF1/CIP1) by miRNAs in bladder cancer cells, KDM5B promoted glioma proliferation partly via regulation of the expression of p21., the non-calcemic 1,25(OH)2D3 analogue (EB1089), induces BRCA1 association with the vitamin D receptor...to enhance CDKN1A expression, Results revealed a novel interplay between IKKepsilon, CHEK1 and p21 signaling in survival of ovarian cancer cells., Deficiency of p21 renders tumor cells more susceptible to Polo-like kinase 1 inhibition by showing a pronounced mitotic arrest, DNA damage and apoptosis., Data suggest an association of ANKHD1 (Ankyrin repeat and KH domain-containing protein 1) protein with p21 (WAF1/CIP1) promoter region., These findings support a model in which in human cells a balance between ATM-Chk2-p53 and the ATR-Chk1 pathways modulates p21(Waf1) protein levels in relation to cytostatic and cytotoxic doses of DNA damage., Results show that lncRNA ANRIL plays a key role in non-small cell lung cancer (NSCLC) development by associating its expression with survival in patients with NSCLC through silencing of KLF2 and P21 transcription., Through its interference with the LKB1-p53-p21/WAF1 pathway expression., In a mouse tumor xenograft model Lack of p21 protein increased sensitivity to the apoptotic effects of the combination of tetrandrine and chloroquine., Although its expression increases in patients with N1 regional metastasis, the loss of p21{WAF1/CIP1} does not seem to have any relationship with the clinical and pathological variables of the tumors., Studies performed genotyping analyses of eight functional CDKN1A p21, oncoprotein p53, TP53BP1 protein and tumor protein p73 single nucleotide polymorphisms (SNPs) in 330 gastric cardia adenocarcinoma (GCA) cases and 608 controls in a Chinese population., Data indicate the role of cyclin-dependent kinase inhibitor 1A (p21) and interleukin enhancer binding factor 3 (ILF3) pathway in mediating the anti-leukemic activity of sodium dichloroacetate (DCA) in oncoprotein p53null leukemic cells., HOTAIR served as an onco-lncRNA in cervical cancer which could enhance various aggressive biological behaviors. Moreover, we proved that HOTAIR execute its functions mainly through inhibiting the p21 expression, TLX functions as a potent suppressor of oncogene-induced senescence in prostate cancer via its transcriptional co-regulation of the CDKN1A (p21(WAF1) (/) (CIP1) ) and SIRT1 genes, phenotype is due to a prolonged G1/S transition via decreasing DICER-dependent biogenesis of miRNA let-7, which increased the p21(Waf1/Cip1)/p27(Kip1) levels, A major implication of our studies is that inhibition of miR-520g or restoration of p21 expression may have considerable therapeutic potential to overcome drug resistance in colorectal cancer patients, especially in those with mutant p53., The cancer-associated variant of p21cip1 may contribute to the loss of cell cycle control in neurons that may lead to Alzheimer-type neurodegeneration., miR-93 stimulated cell proliferation, migration, and invasion through the oncogenic c-Met/PI3K/Akt pathway and also inhibited apoptosis by directly inhibiting PTEN and CDKN1A expression in human hepatocellular carcinoma., These results suggest that INMAP might function through p53/p21 pathways., Findings suggest that the regulation of c-Myc in breast cancer cells is dependent on the molecular subtype, and that beta-catenin-mediated regulation of c-Myc and p21 may control the balance of cell death and proliferation in breast cancer., results suggested that the senescence programs mediated by p15(INK4b), p16(INK4a) and p21(Waf1/Cip1) were activated during the stage of cervical intraepithelial neoplasia and squamous cell carcinoma, Our findings suggest that alteration of p16, p14, p27, p21, and p53 status may contribute to carcinogenesis and the clinical behavior of HPV-negative adenocarcinoma of the uterine cervix, Data suggest that miR-130 plays an role in the repression of CDKN1A by hypoxia. miR-130 enhances hypoxia-induced smooth muscle proliferation., The study suggest that the Cip/Kip family may have a role as a molecular mechanism of carcinogenesis in early glottic cancer., miR-93 was increased in polycystic ovary syndrome granulosa cells and targeted CDKN1A to promote proliferation and cell cycle progression., Silence of nucleostemin inhibit cell proliferation through up-regulating p21 expression and nucleostemin may be involved in the pathogenesis of esophageal squamous cell carcinoma., The control operated by the cell cycle machinery on MEF2 stability contributes to the downregulation of CDKN1A and entry into S phase in human fibroblasts., There was a weak linear trend between risk of infection after exposure and increasing p21 gene expression, but again only in one experiment, By down-regulating Bak, P53, P21, BRCA1, BCL-Xl., Caffeic acid phenethyl ester induced cell cycle arrest and growth inhibition in prostate cancer cells via regulation of Skp2, p53, p21Cip1, and p27Kip1., Single nucleotide polymorphism in CDKN1A gene is associated with colorectal cancer., Mutant p53 expression decreased gradually from cancerous to normal mucosae, whereas p21(CIP1/WAF1) expression displayed an opposite trend, LIF/p21 signaling cascade as a novel tumor suppressive-like pathway in melanoma, acting downstream of TGFbeta to regulate cell cycle arrest and cell death, further highlight new potential therapeutic strategies for the treatment of cutaneous melanoma, Manipulation of the miR-221/222-Ets-1-p21 pathway may offer a novel strategy for treatment of endothelial apoptosis., Studies on human keratinocytes recognized that loricrin expression was inversely related to the expression of the cyclin-dependent kinase inhibitor p21, paclitaxel may be an effective anticancer agent through regulating the expression of p21(Cip1) for the treatment of BRAF mutant melanoma cells resistant to BRAF inhibitors., our study identifies a pair of miRNA-dsRNA mediating endogenous p21 overexpression., p21 may play a key role in apoptosis, proliferation, cell cycle arrest, and antioxidant activity in UVB-irradiated human HaCaT keratinocytes., findings suggest that down-regulation of BANCR contributes to the proliferation of colorectal cancer cells, at least in part, through the regulation of p21 protein., Long non-coding RNA GAS5 down-regulation reduced the YBX1 protein level, which decreased YBX1-transactivated p21 expression and abolished G1 phase cell cycle arrest in stomach cancer., the hydroxyl group of Tyr151 in p21 acts as a tethering point for ideal packing and surface recognition of the peptide interface, increasing the binding affinity of p21 for PCNA., p21(CIP1/WAF1) has a role in decreasing chondrogenic differentiation potential in synovial membrane progenitor cells, CTDSP2 induces p21(Cip1/Waf1) through increasing the activity of Ras., USP1, p21 and Spartan are translesion DNA synthesis regulators. (Review), Loss of p21 in HCT116 Cells Is Associated with Accumulation of DNA Double-Strand Breaks., miR-20a interferes with the colonic epithelium homeostasis by disrupting the regulation of Myc/p21 by TGF-beta, which is essential for its malignant transformation., A partially methylated or unmethylated RASSF1A promoter as well as elevated serum AFP level or methylation of p21 in addition to elevated serum AFP level might be associated with poor prognosis in patients with hepatocellular carcinoma., We conclude that Bz-surviving MM cells display a GRP78(HIGH)/p21(HIGH)/CDK6(LOW)/P-Rb(LOW) profile, and these markers may identify quiescent MM cells capable of fueling recurrences., stratified analysis showed rs1059234 polymorphism was greatly associated with the risk of squamous cell carcinoma of head and neck., Together, these data suggest that Curcumin inhibits growth of PC via miR-208-mediated CDKN1A activation, Chromatin immunoprecipitation analysis revealed interaction between SOX9 and the specific region of the p21WAF1/CIP1 promoter. Data suggest that SOX9 is a potential therapeutic target in cervical carcinoma, that transactivates p21WAF1/CIP1, Data show that the protein phosphatase 2A (PP2A)/c-jun N-Terminal Kinase (JNK)/Sp1 transcription factor/CDK1 kinase pathway and the autophagy/cyclin kinase inhibitor p21 pathway participated in G2/M cell cycle arrest triggered by PP2A inhibitors., These results reveal a novel mechanism by which MAF1 and Pol III regulate the activity of the CDKN1A-encoding gene transcribed by Pol II., In G28 cells, a dosedependent induction of CDK2, p21 and cyclin D was observed between 10 and 50 microM roscovitine after 72 h, however, at the highest concentration of 100 microM, all investigated genes were downregulated., Combined immunohistochemistry of PLK1, p21, and p53 can predict the TP53 status of breast cancer patients., UTD1, a genetically engineered epothilone analog and a new microtubule inhibitor, activated p53 as a transcription factor at low concentrations demonstrated by its enhanced transcriptional activity and accumulation of p21, which led to cell cycle arrest, Blocking TGFBR1 receptor up-regulated p21 expression while inhibiting breast tumor cell growth., Low p21 expression predicated tumor recurrence and poor prognosis in bladder cancer., These findings point to (i) the relevance of CS-related mechanisms in Hodgkin lymphoma , and to (ii) the prognostic value of a simple, reproducible, and low-cost immunohistochemical evaluation of p16(INK4a) and p21(CIP1/WAF1) expression., NGP-1 promotes cell cycle progression through the activation of the p53/p21(Cip-1/Waf1) pathway., Data indicate that resveratrol plus curcumin inhibits Hedgehog-Gli1 components in p21Waf1/Cip1 dependent manner., JunB is likely to be a key target of c-Abl in expression of p21 in Adriamycin-induced DDR., Results demonstrate an antagonistic relationship between pUL27 and pUL97 activities centering on the host p21Cip1., This study indicated that miR-4295 negatively regulates CDKN1A and promotes proliferation and invasion of ATC cell lines. Thus, miR-4295 may represent a potential therapeutic target for ATC intervention., These observations illustrated that miR-106b could induce cell radioresistance by directly targeting PTEN and p21., The rs1059234 C > T polymorphism was associated with increased risk of squamous cell carcinoma of the head and neck (SCCHN.), This case-control study was designed to analyse the association Single nucleotide polymorphisms (SNPs) of p53 rs1042522, MDM2 rs2279744 and p21 rs1801270 and retinoblastoma (RB) in a Chinese Han population., Data show that all the chelators up-regulated cyclin dependent kinase inhibitor 1A (p21/CIP1/WAF1) mRNA in the five tumor cell-types, but either upregulated or downregulated total p21 protein levels., INO80 complex negatively regulates p21 expression in a p53-mediated mechanism and is implicated in cell cycle phase G2/M arrest and abnormal chromosome stability., Plk3 is involved in the inhibition of cell proliferation and tumorigenesis, which may occur via interactions with p21., Data suggest that HOXA-AS2 could be an oncogene for GC partly through suppressing P21, PLK3, and DDIT3 expression., downregulation of these genes through the p53-p21-DREAM-CDE/CHR pathway appears to be a principal mechanism for G2/M cell cycle arrest by p53., Phosphorylation of p53 by LRRK2 induces p21(WAF1/CIP1) expression and apoptosis., LRH-1 drives colon cancer cell growth by repressing the expression of the CDKN1A gene in a p53-dependent manner., Data showed that miR-423 was up-regulated in colorectal cancer (CRC) tissues promoting cell proliferation. Cip1 mediated the function of miR-423, and its overexpression reversed the augmented effect of miR-423 on cell proliferation., PRMT6 methylates tumor cell p21 at arginine 156 and promotes phosphorylation of threonine 145 on p21, increasing the cytoplasmic localization of p21 and inducing resistance to anticancer drugs., Data show CGK733 induced microtubule associated protein LC3B formation upstream of AMP-activated protein kinase and protein kinase RNA-like endoplasmic reticulum kinase/CCAAT-enhancer-binding protein homologous protein pathways and p21 Cip1 expression., p21WAF1 regulates the early stages of drug-induced apoptosis in B-cell precursor acute lymphoblastic leukemia cells and significantly modulates their sensitivity to vorinostat., p21 may function as a regulator of transcriptional factors other than the inhibitor of cell cycle progression in the cartilage tissue, accumulation of HDAC4 induced by fibrillar collagen matrices in the nucleus via co-localization of PP1alpha, leads to repression of the mRNA/protein of p21 and in turn promotes the proliferation and migration of epithelial ovarian cancer cells, Suggest that the p53-p21-DREAM-CDE/CHR pathway regulates p53-dependent repression of Survivin, CDC25C, and PLK1 in HCT116 cells., These results suggest that p21(Waf1/CIP1) and Hus1 play crucial roles in the generation and transmission of bystander damage signals after low-dose alpha-particle irradiation., Overexpression of miR-512-5p led to the decrease of p21 protein., tumor suppressive function of HPCAL1 was dependent on p21 in hepatocellular carcinoma, Clioquinol suppressed cell cycle progression in the S-phase in SMMC-7721 hepatoma cells via the p21, p27-cyclin E,A/Cdk2 pathway., These data collectively suggest a novel mechanism involving CSLC-specific targeting by evodiamine and its possible use to the therapy of breast cancer., Data show that interaction of cyclin-dependent kinase inhibitor 1A (p21 Cip1) with poly(ADP-ribose) polymerase-1 (PARP-1) is mediated by poly(ADP-ribose) (PAR)., Data suggest that cell cycle-dependent kinase inhibitors CDKN1A/p21 and CDKN2C/p18 facilitate cell cycle entry/cell proliferation of quiescent adult human pancreatic beta cells in primary culture (from tissues obtained from organ donors)., It was concluded that over-activation of the mTORC1/4E-BP1/p21 pathway is a frequent and clinically relevant alteration in head and neck squamous cell carcinomas., Foxo3 circular RNA retards cell cycle progression via forming ternary complexes with p21 and CDK2., prolactin activation of Stat5 results in the formation of a complex between phospho-Stat5 and BRCA1. Formation of this complex does not interfere with nuclear translocation or binding of BRCA1 to the p21 promoter, these results demonstrate complex links between different signaling cascades in stressed hMESC, implicating ERK, p38 and JNK in regulation of the premature senescence via p53/p21/Rb pathway., demonstrated that patients with the LMP-7 CA/AA genotypes were more likely to have advanced fibrosis scores than those bearing the CC genotype,
OFFICIAL_GENE_SYMBOL CDKN1A,
SP_COMMENT function:May be the important intermediate by which p53 mediates its role as an inhibitor of cellular proliferation in response to DNA damage. Binds to and inhibits cyclin-dependent kinase activity, preventing phosphorylation of critical cyclin-dependent kinase substrates and blocking cell cycle progression., induction:By p53, mezerein (antileukemic compound) and interferon beta., PTM:Phosphorylation of Thr-145 by Akt or of Ser-146 by PKC impairs binding to PCNA., similarity:Belongs to the CDI family., tissue specificity:Expressed in all adult human tissues, with 5-fold lower levels observed in the brain.,