Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
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MDM2 proto-oncogene(MDM2) MDM2 proto-oncogene(MDM2) Related Genes Homo sapiens
CHROMOSOME 12,
CYTOBAND 12q14.3-q15,
ENSEMBL_GENE_ID ENSG00000135679,
GENERIF_SUMMARY mdm2 has binding sites for phosphorylation by CK2, protein interaction mapping with mouse p19ARF, a regulatory loop exists in which Hdm2 regulates the intracellular localization of Hdmx, and nuclear Hdmx regulates several functions of Hdm2 (ubiquitin ligase activity and p53 nuclear export)., higher expression in childhood leukemias with poor prognosis compared to long-term survivors, Normal cells may induce full-length MDM2 in response to oncogenic challenges to protect against premature cell cycle progression. MDM2 is regulated by p53 especially durnig embryogenesis where MDM2 function is inhibited., findings suggest that amplification and overexpression of HMGIC and possibly MDM2 might be important genetic events that may contribute to malignant transformation of benign pleomorphic adenoma, absence of nucleolar or nucleoplasmic p14ARF/Hdm2 complexes in Reed Sternberg cells in Hodgkin's lymphoma associated with expression of alternatively spliced Hdm2 transcripts, MDM2 overexpression correlates with favorable prognosis in human breast cancer, p53 ativation by nitric oxide involves down-regulation, role for IGF-I in the regulation of the MDM2/p53/p21 signaling pathway during DNA damage, Antisense of MDM2 enhance therapeutic efficiency of irinotecan in colon cancer, Akt enhances Mdm2-mediated ubiquitination and degradation of p53., description of a novel MDM2 binding interface in p53 that plays a regulatory role in MDM2-dependent ubiquitination of p53, Novel splice variants identified in pediatric rhabdomyosarcoma tumors and cell lines, MDMX, when exceedingly overexpressed, inhibits MDM2-mediated p53 degradation by competing with MDM2 for p53 binding, Cirrhotic livers reveal genetic changes in the MDM2-P14ARF system of cell cycle regulators., promoter usage of mdm2 gene in human breast cancer, Phosphorylation of HDM2 by Akt, and protein binding, summarize the current understanding of post-translational modifications and their effect on conformation-based functional relationship between Mdm2 and p53, MDM2 induces NF-kappaB/p65 expression transcriptionally through Sp1-binding sites; a novel, p53-independent role of MDM2 in doxorubicin resistance in acute lymphoblastic leukemia., Cyclin G expression also results in reduced phosphorylation of human Hdm2 at S166., p53 Stability and activity is regulated by Mdm2-mediated induction of alternative p53 translation products., expression significantly correlated with favorable prognosis in esophageal squamous cell carcinoma in p53-negative patients but not p53-positive patients, MDM2 can inhibit PCAF-mediated p53 acetylation and activation., MDM2 inhibition of p53 induces E2F1 transactivation via p21, RNA polymerase III transcription can be derepressed by hdm2, Multiple interacting domains contribute to p14ARF mediated inhibition of MDM2, implications of phosphorylation in p53 regulation, Data suggest a model in which p53 directly recruits a TRRAP/acetyltransferase complex to the mdm2 gene to activate transcription. In addition, this study defines a novel mechanism utilized by the p53 tumor suppressor to regulate gene expression., MDM2 has been characterized as a protein that binds to and facilitates degradation of the tumor suppressor p53. Splice variants of MDM2 transcripts have been identified in both tumors and normal tissues., Hypophosphorylation of Mdm2 augments p53 stability. The degree of conservation in the central acidic domain of mouse and human Mdm2 proteins is high., The candidate tumor suppressor ING1b can stabilize p53 by disrupting the regulation of p53 by MDM2., MAPK as an upstream regulator of mdm2 expression, MDM2 is not required for p53 proteasomal degradation regulated by NADPH quinone oxidoreductase 1, p14ARF promotes accumulation of (H)Mdm2 conjugated to the small ubiquitin-like protein SUMO-1., Results describe the thermodynamic and kinetic-binding parameters for the interaction between MDM2 and p53 proteins., MDM2 ubiquitination is enhanced by MDMX, Mdm2 is sumoylated during nuclear translocation by RanBP2 and then further sumoylated once in the nucleus by PIASxbeta and PIAS1, Overexpression of mdm2 was seen predominantly in blastoid mantle cell leukemia, seemed unrelated to gain of chromosome 12, did not reflect a high proliferative rate, but might indicate an alternative mechanism of inactivating p53., acetylation of p53 inhibited by its ubiquination, MDM2 can promote p53 deacetylation by recruiting a complex containing HDAC1. Wild-type HDAC1 and MDM2 deacetylate p53 synergistically., The combined expression of adenovirus E1A, Ha-RasV12, and MDM2 is sufficient to convert a normal human cell into a cancer cell., Ubiquitination and degradation of p53 are largely controlled by Mdm2, an oncogenic E3 ligase., role of p53 binding domain in p53 regulation, Data provide evidence of a role for MDM2 and CDK4 in the pathogenesis of carcinosarcoma., in glioblastoma multiforme patients a complex relationship exists between the Mdm2 expression and age, Mdm2-mediated p53 ubiquitination is suppressed by HIF-1 alpha, which blocks Mdm2-mediated nuclear export of p53, La antigen dependent activation of mdm2 translation might represent an important molecular mechanism involved in BCR/ABL leukemogenesis, These data strongly suggest that Mdm2 functions as the ubiquitin ligase toward hNumb and that it induces its degradation in intact cells., Overexpression of the Mdm2 gene product may be important in the pathogenesis of penile verrucous carcinoma since Mdm2 is a negative regulator of p53, It appears, that MDM2 overexpression, which may be p53-dependent, or also p53-independent plays an important role in leukemogenesis and/or disease progression., two upstream open reading frames of oncogene mdm2 may play a fundamental role in regulating expression of the mdm2 gene, p53-independent activation of the hdm2-P2 promoter through multiple transcription factor response elements results in elevated hdm2 expression in estrogen receptor alpha-positive breast cancer cells., ubiquitination of MDM2 is cell cycle-regulated and MDM2 may play a role in cell cycle progression, Mdm2 physically associates with IGF-1R and that Mdm2 causes IGF-1R ubiquitination in an in vitro assay. Mdm2 serves as a ligase in ubiquitination of the IGF-1R and thereby causes its degradation by the proteasome system., MDM2 promotes ubiquitination and degradation of MDMX, MDM2 regulates hdmx protein stability, Ligase dead mutants of Mdm2 did not act in a dominant negative manner to reactivate p53 and they are not oncogenes in human mammary epithelial cells., MDM2 is regulated and degraded by GCL-1, colocalization of a nonshuttling p53 with MDM2 either in the nucleus or in the cytoplasm is sufficient for MDM2-induced p53 polyubiquitination but not degradation., MDM2 has a role in DNA damage-induced MDMX degradation, study of MDM2 protein binding to the N-terminal domain of p53, HdmX is actively involved in the degradation of both p53 and Hdm2., Results imply that the current paradigm for understanding Mdm2 action during oncogenesis is incomplete, and its splice variants contribute to human cancer., PTEN inhibits MDM2 and protects p53 through both p13k/Akt-dependent and -independent pathways in ALL., The expression and structure of HDM2 in HL cell lines was studied. Several different spliced hdm2 transcripts (mdm-sv) including five new variants lacking a functional p53 binding site were characterized., Mdm2 is a regulator of cell growth and death [review], interaction with nucleic acids interferes with both Hdm2/Hdm2 complex formation and auto-ubiquitination of Hdm2 in vitro; although binding of Hdm2 to p53 is not inhibited by nucleic acids, Hdm2-mediated ubiquitination of p53 is significantly decreased., MDM-2 overexpression can block UV-induced cell cycle arrest and apoptosis by inhibiting P53 transcriptional activity, L11 functions as a negative regulator of HDM2 and there might exist in vivo an L11-HDM2-p53 pathway for monitoring ribosomal integrity, MDM2 amplification in soft tissue sarcoma patients was associated with a prognosis better than that of patients without the amplification. of the tumors with an MDM2 amplification, 40% also experienced loss of heterozygosity at 12q14-15., MDM2 directly inhibits p21waf1/cip1 function by reducing p21waf1/cip1 stability in a ubiquitin-independent fashion, results show that low levels of Mdm2 activity induce monoubiquitination and nuclear export of p53, whereas high levels promote p53's polyubiquitination and nuclear degradation, overexpression is related to the tumorigenesis and/or tumour progression of salivary gland neoplasms, MDM2 acts as a transcriptional factor to modulate expressions of other genes involved in cell cycle regulation and transformation and was hypothesized that MDM2 directly affected NF-kappaB expression and function in a P53-independent manner., Upregulation of p14ARF paralleled with MDM2 inhibition contributes to p53 accumulation in the nucleus in radiation-treated breast cancer cells., MDM2 may regulate p53, depending on its levels in the cell., Data report the effects of peptide binding on the N-terminal p53-binding domain of human MDM2., No correlation between p53 accumulation and survival in bilharziasis associated bladder squamous cell carcinoma., MDM2 functions as a negative regulator of p21, an effect independent of both p53 and ubiquitination, MDM2 regulates the stability of PCAF by ubiquitinating and degrading this protein, results identify an interferon-responsive protein kinase family as a novel modifier of two components of the p53 pathway, MDM2 and p21(WAF1), acetyltransferases may modulate cellular p53 activity not only by modifying p53, but also by inactivating Mdm2, Results show that growth factor stimulation, overexpression of Akt/PKB, or loss of PTEN resulted in enhanced expression of both HIF-1alpha and HDM2., CDK4, MDM2, SAS and GLI genes are amplified in leiomyosarcoma, alveolar and embryonal rhabdomyosarcoma, Data reveal that controlled MDM2 degradation is an important new step in p53 regulation., potential of p53-C277Y to up-regulate MDM2 expression was similar to wild-type p53, Mdm2 in female patients is an independent prognostic factor, associated with shorter survival in brain glioma., the MDM2-L5-L11-L23 complex functions to inhibit MDM2-mediated p53 ubiquitination and thus activates p53, These results reveal that ribosomal protein L23 is another regulator of the p53-MDM2 feedback regulation involved in cell growth., Data show that, when overexpressed, ribosomal protein L23 inhibits HDM2-induced p53 polyubiquitination and degradation and causes a p53-dependent cell cycle arrest., MDM2 gene spans approximately 33 kb and is divided into 12 exons., Ras appears to attenuate p53 in SW480 cells by two independent regulatory mechanisms, the one leading to increased Mdm2-dependent p53 degradation and the other leading to a decrease in p53 transcription., Review of MDM2 which inhibits p53 degradation in head and neck cancers, Epstein barr virus can indirectly enhance mdm2 gene expression in tumor cells that express this gene., the central acidic domain of MDM2 is critical in inhibition of retinoblastoma-mediated suppression of E2F and cell growth, MDM2-p73-P14ARF pathway is involved in the progression of bladder cancer to a more malignant and aggressive form., identify Ser-166, a site previously reported as an AKT target, and Ser-188, a novel site which is the major site of phosphorylation of MDM2 by AKT in vitro, The RING domain of MDM2 mediates histone ubiquitylation and transcriptional repression., role of Cul4A in the MDM2-mediated proteolysis of p53, A single nucleotide polymorphism is found in the MDM2 promoter and is shown to increase the affinity of the transcriptional activator Sp1, resulting in higher levels of MDM2 RNA and protein and the subsequent attenuation of the p53 pathway., The level of MDM2 gene expression was related to the prognoses of the patients but not to FAB subtypes of acute leukemias., Data suggest that MTBP differentially regulates the activity of MDM2 towards two of its most critical targets (itself and p53) and in doing so significantly contributes to MDM2-dependent p53 homeostasis in unstressed cells., finding that MYCN directly modulates baseline MDM2 levels suggests a mechanism contributing to the pathogenesis of neuroblastoma and other MYC-driven malignancies through inhibition of MYC-stimulated apoptosis., Mouse cells deficient for MK2 show reduced Mdm2 phosphorylation and elevated levels of p53 protein., Alternative MDM2 splicing is highly associated with lung cancer., Mdm2 activity could activate p53 tumor suppression REVIEW, MDM2 has oncogenic transformational activities independent of p53--REVIEW, MDM2 splice variant expression has been associated with advanced neoplastic disease--REVIEW, MDM2 oncogene is overexpressed in more than forty different types of malignancies--REVIEW, Regulation of the nuclear export of hdm2 mRNA provides a mechanism whereby mitogen-stimulated cells avoid p53-dependent cell cycle arrest or apoptosis by maintaining the dynamic equilibrium of the Hdm2-p53 feedback loop, The overexpression of MDM2 oncogene related to the poor status and poor prognosis of patients with childhood NHL,correlated with B status and the involved extranodal sites and the increased serum LDH level, p73, through HDM2, can oppose p53 tumor suppressor function and possibly contribute to tumorigenesis, Nbs1 is a novel p53-independent Mdm2 binding protein and links Mdm2 to the Mre11-Nbs1-Rad50-regulated DNA repair response, The abundant expression of double-minute protein 2 (MDM2) in rheumatoid arthritis may be a contributing factor to the hypoapoptotic phenotype of lining tissue through its capacity to downregulate p53 levels and effects., MDM2 may have implications for glioma cell death susceptibility, Mdm2 and mdmx prevent ASPP1 and ASPP2 from stimulating the apoptotic function of p53 by binding and inhibiting the transcriptional activity of p53., sites important for Hdm2-mediated ubiquitination of Hdmx after double-strand break induction, alpains participate in the down-regulation of Mdm2 in the epidermis very rapidly after UV irradiation., p53, Bax, Bcl-2 and Mdm2 mRNA expression levels correlate with the malignant transformation of the uterine cervix, protection of p53 from MDM2 by PTEN and the damage-induced activation of PTEN by phosphorylated p53 leads to the formation of an apoptotic amplification cycle in which p53 and PTEN coordinately increase cellular apoptosis, HDM2 negatively affects the Chk2-mediated phosphorylation of p53., expression of p53, MDM2, and p21Waf1 suggests a role for these oncoproteins in the regulation of endometrioma cell growth, but not in adenomyosis, MdmX can affect post-translational modification and stability of Mdm2 and p53 activity through interaction with ARF, beta-arrestin has a role in ubiquitination and down-regulation of the insulin-like growth factor-1 receptor by acting as adaptor for the MDM2 E3 ligase, TP53 mutation has only a limited role in the transformation of lymphoma to diffuse large B-cell lymphoma, exerting a heterogeneous influence upon phenotypic change. In contrast, dysregulation of MDM2 is frequent., overproduction of Mdm2, resulting from a naturally occurring SNP, inhibits chromatin-bound p53 from activating the transcription of its target genes., Results suggest that impaired deubiquitination of Hdmx/Hdm2 by HAUSP contributes to the DNA damage-induced degradation of Hdmx and transient instability of Hdm2., besides tumor protein p53 alterations, MDM2 gene deregulation seems to be an important event in hepatocarcinogenesis, analysis of the more open conformation of the binding cleft of MDM2N (non-liganded), Data show that expression of the ErbB-4 ICD fragment leads to its constitutive association with and tyrosine phosphorylation of Mdm2., deletion of Mdm4 enhances the ability of Mdm2 to promote cell growth and tumor formation, indicating that Mdm4 has antioncogenic properties when Mdm2 is overexpressed, GSK3-dependent phosphorylation of Mdm2 regulates p53 abundance, ATM directly activates p53 while activating a safe-lock mechanism to inactivate the negative regulators of p53, Mdm2, and Mdmx [review], ARF may regulate p53 acetylation and stability in part by inhibiting tripartite motif-containing 28-MDM2 binding, the p14ARF-p53-MDM2 pathway has a role in development of oral squamous cell carcinoma, 2 promoter polymorphisms of MDM2 and evaluated their associations with risk of lung cancer, p53-mdm2 binding is subtler than previously thought and involves global contacts such as multiple "non-contiguous" minimally structured motifs instead of being localized to one small helix mini-domain in p53 TAD, The E3 ligase activity of MDM2 is redirected to MDMX after DNA damage and contributes to p53 activation., T309G polymorphism for MDM2 significantly decreases the age of onset for ALL in the pediatric population, particularly within Caucasian and black pediatric communities, MDM2 stabilizes E2F1 protein through the E2F1 ubiquitination pathway., Studies reported the discovery of a third promoter (designated P3) in intron 3 of MDM2 gene, which contains a TATA-box element and p53-DNA-binding sequences., the p53 and MDM2 promoter polymorphisms do not appear to play a role on age of colorectal cancer onset in Lynch syndrome, HIPK2 contributes to drug-induced modulation of MDM2 activity at transcriptional (through p53Ser46 phosphorylation) and posttranscriptional (through p53-independent subcellular re-localization and proteasomal degradation) levels., the p53-HDM2 interaction can be inhibited by a newly isolated hexylitaconic acid from the marine-derived fungus, Arthrinium, Studies of MDM2 in more than 2000 breast carcinomas show that MDM2 is an independent negative prognostic marker., Genetic polymorphisms in cell cycle regulatory genes MDM2 and TP53 contribute to the risk of developing lung cancer., The MDM2 promotes Rb degradation in a proteasome-dependent and ubiquitin-independent manner., These findings suggest that overexpression of Mdm2 can perturb a RB pathway regardless of the p53 gene status, promoting carcinogenesis., MDM2 has critical roles in the regulation of p21 and E2F1 expression, stability and function [review], identification of a second binding site helps stabilize the interaction between HDM2 and p53 during p53 degradation, MDM2 -309 allele and genotype frequencies did not differ between cases and controls, and ORs for breast cancer were close to the null in African-Americans and Whites., MDM2 antagonists alone or in combination with chemotherapeutic drugs may offer a new treatment option for B-CLL., N-terminal domain of USP7 binds two closely spaced 4-residue sites in both p53 and MDM2, falling between p53 residues 359-367 and MDM2 residues 147-159., Our data indicate that MDM2-SNP309 is a modifier of the age at colorectal cancer onset for patients whose tumors have a wild-type p53 gene., IFIX alpha1 isoform functions as a tumor suppressor by repressing HDM2 function, Results indicate that the MDM2 G/G genotype of SNP309 is associated with lung cancer risk with an odds ratio of 1.62 (95% CI, MdmX may have different roles in the regulation of Mdm2 activity for ubiquitination of pRB and p53, analysis of the role of p53 substrate conformation in controlling MDM2-dependent ubiquitination of p53 and identification of a link between substrate misfolding and susceptibility to ubiquitination, p90Rsk-mediated modulation of Hdm2 nuclear is linked to cytoplasmic shuttling with the diminished ability of p53 to regulate cell cycle checkpoints that ultimately leads to transformation, HDM2 can selectively down-regulate the transcription function of p53 without either degrading p53 or affecting the interaction of p53 with target promoters, Jab1 is required to remove post-translationally modified p53 in coordination with mdm2, Data show that nuclear accumulations of p53 and Mdm2 are accompanied by reductions in c-Abl and p300 in zinc-depleted human hepatoblastoma cells., study showed that MDM2 amplification and overexpression might be an early event in the growth of human gliomas, interaction of free arrestins with JNK3 and Mdm2 and their ability to regulate subcellular localization of these proteins may play an important role in the survival of photoreceptors and other neurons, Review. An alternative splice form of c-H-ras, called p19ras, is a positive regulator of p73beta via Mdm2. Implications for this previously unidentified means of regulation are discussed in light of tumor suppression and are extended to p53 and p63., levels are reduced by nucleolin, L11, unlike L5 and L23, differentially regulates the levels of ubiquitinated p53 and MDM2 and inhibits the turnover and activity of MDM2 through a post-ubiquitination mechanism, Collectively, our results suggest that a loss of the cisplatin sensitivity is at least in part due to a lack of cisplatin-induced p53 phosphorylation, and p73 might cooperate with MDM2 to be involved in this process., Among homozygous carriers of the common MDM2 SNP309 allele, a mutant p53 status (risk ratio of death = 2.33, 95% CI = 1.08 to 5.03)and aberrant p53 protein expression(RR = 2.61, 95% CI = 1.22 to 5.57)in breast tumors were associated with poor survival., Data suggest that the G-allele of SNP309 accelerates colorectal tumour formation only in women., MDM2-single nucleotide polymerase 309 favours tumour selection of non-dominant negative P53 mutations in colorectal cancer, which also show an earlier age of tumour onset., PCNA, L2DTL and the DDB1-CUL4A complex play critical and differential roles in regulating the protein stability of p53 and MDM2/HDM2 in unstressed and stressed cells., Although the interaction between the N-termini of mdm2 and p53 blocks the transactivation activity of p53, the interaction between the central domain of mdm2 and the core domain of p53 is critical for the ubiquitination and degradation of p53., p53 binding to the central domain of Mdm2 is regulated by phosphorylation, MDM2 is therefore considered one of the mineralocorticoid-responsive genes that regulates cell proliferation of vascular smooth muscle cell (VSMCs) induced by MR-mediated aldosterone stimulation., These results suggest that p70S6K1 regulates turnover of HDM2 protein for cancer development., Gene amplifications are important prognostic markers for soft tissue sarcomas., Hdmx is an important determinant of the outcome of P53 activation, The MDM2 promoter SNP309 is associated with the presence of hepatocellular carcinoma in Japanese patients with chronic hepatitis C., Study evaluated Pirh2, MDM2, p53 and p21 expression after DNA damage using cancer cell lines containing wildtype, mutant and null p53 and found that unlike MDM2, Pirh2 expression was not affected by the presence of wildtype p53 in the cancer cells., Results report the solution structure of the C2H2C4 RING domain of Hdm2(429-491), which reveals a symmetrical dimer with a unique cross-brace zinc-binding scheme., A novel role for MDM2 in regulating cell adhesions by a mechanism that involves degrading and down-regulating the expression of E-cadherin via an endosome pathway., The cooperative effects of phenotypes determined by mdm-2, p53, and bcl-2 expression may predict survival in patients with muscle-invasive TCC of the bladder, TP53 germline mutation carriers with SNP309 G allele have earlier onset of tumours; higher prevalence of MDM2 SNP309 homozygous carriers in TP53-negative group suggests allele contributes to cancer susceptibility in Li-Fraumeni syndrome & related families, insulin-like growth factor-1 alters Mdm2-mediated GRK2 degradation, leading to enhanced GRK2 stability and increased kinase levels, When the p73 and MDM2 polymorphisms were combined, the risk of lung cancer increased in a dose-dependent manner as the number of variant alleles increased, Stress-induced HDM2(ALT1) regulates HDM2 at two levels, RNA and protein, further modulating the p53-HDM2 interaction or interactions of HDM2 with other cell cycle regulatory proteins., Alternate forms of MDM2 are detected after UV irradiation. Alternate forms of MDM2 place selective pressure on the cells to acquire additional alterations in the p53 pathway., the reduction of KAP1 levels promotes p53-dependent p21 induction and inhibits cell proliferation in actinomycin D-treated cells., analysis of mechanism of formation of the principal MDM2 isoforms, differential effects of p53 on the production of these isoforms, and differential abilities of human MDM2 isoforms as regulators of the MDM2/TSG101 and p53/MDM2 feedback control loops, MDM2 single nucleotide polymorphism accelerates familial breast carcinogenesis independently of estrogen signaling, MDM2 T309G polymorphism is associated with bladder cancer, Results indicate the G allele of MDM2 SNP309 might have a protective effect on disease development in HNPCC patients and that age of diagnosis of CRC is not associated with MDM2 SNP309 or TP53 R72P either as single SNPs or combined., Cancer-associated missense mutations targeting MDM2's central zinc finger disrupt the interaction of MDM2 with L5 and L11., AURKA and MDM2 were identified as interesting novel amplified genes in juvenile angiofibromas, p53 mediates the suppression of TR3 on MDM2 at both transcriptional and post-transcriptional level and suggest TR3 as a potential target to develop new anticancer agents that restrict MDM2-induced tumor progression., functions of the extreme C-terminus of MDM2 can be provided by MDMX, Mdm2 RING domain C-terminus is required for supramolecular assembly and ubiquitin ligase activity, 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., p72 RNA helicase may not only be involved in the p53-Mdm2 regulatory loop, but also profoundly impact on the transcriptome through various CBP/p300 and P/CAF interacting proteins., Mdm2 and TAFII250 associate in cultured cells; the acidic domain of MDM2 is required for TAFII250-stimulated ubiquitylation and degradation of p53., 5-FU treatment triggers a ribosomal stress response so that ribosomal proteins L5, L11, and L23 are released from ribosome to activate p53 by ablating the MDM2-p53 feedback circuit, Both kinetics and free energy landscape analyses indicate that bound MDM2 unfolds in the order of p53 unbinding, tertiary unfolding, and finally secondary structure unfolding., S7 binds to MDM2, in vitro and in vivo, and the interaction between MDM2 and S7 leads to modulation of MDM2-p53 binding by forming a ternary complex among MDM2, p53 and S7., Review discusses the important regulatory roles of MDMX during the p53 response to ribosomal stress., BOX-V motif of p53 has evolved the capacity to bind to enzymes that mediate either p53 phosphorylation or ubiquitination, These findings establish HIPK2 as an MDM2 target and support a model in which, upon nonsevere DNA damage, p53 represses its own phosphorylation at Ser46 due to HIPK2 degradation., Nutlin efficiently stabilized p53 and induced downstream p53 dependent transcription and apoptosis in liposarcoma cells with amplified MDM2 in vitro, Arrestins recruit ERK1/2 and the E3 ubiquitin ligase Mdm2 to microtubulesin cells, similar to the arrestin-dependent mobilization of these proteins to the receptor., analysis of haplotype structure and selection of the MDM2 oncogene in humans, results argue that Mdm2 is needed for full inhibition of Cdk2 activity by p21, thereby positively contributing to p53-dependent cell cycle arrest, Our analysis reveals interactions of HDM2 with the ribosomal translation elongation factor EF1alpha, 40S ribosomal protein S20, tubulins, glyceraldehyde 3-phosphate dehydrogenase, and a proteolysis-inducing factor dermicidin., The -309 SNP in MDM2 is associated with increased MDM2 transcription but there are inconclusive results with respect to breast cancer risk, Colocalization and interaction of MDM2-A and MDM2-B with full-length MDM2 in the nucleus have important physiologic consequences, for example, deregulation of p53 activity., 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, Che-1 as a new Pin1 and HDM2 target and confirm its important role in the cellular response to DNA damage., findings suggest that the MDM2 SNP309 may be a risk factor for the occurrence and advanced neck lymph node metastasis of nasopharyngeal carcinoma in Chinese population, MDM2 overexpression is associated with copy number gains of the MDM2 locus in single tumors, but not with the recently reported MDM2 promoter SNP309., Both ionizing radiation and daunorubicin treatment resulted in concerted protein modulations of Mcl-1, Hdm2 and Flt3., ubiquitination-mediated repression of p53 by Mdm2 acts at least, in part, through inhibiting the sequence-specific DNA binding activity, Nutlin-3 could protect both endogenous and exogenous p53 from MDM2-mediated inactivation, a trimeric protein complex containing p53, Mdm2 and HAUSP can exist in vivo, despite mutually exclusive binding, with Mdm2 serving as a binding mediator for p53 and HAUSP, in this study population, SNP309 affected MDM2 protein level, but had no significant involvement in glioma tumorigenesis, 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, findings suggest that the G/G genotype of the MDM2 polymorphism is associated with worse overall survival among early-stage non-small-cell lung cancer patients, particularly those with squamous cell histology, SNP309 of HDM2 is a frequent event in bladder cancer, related to earlier onset of superficial disease and TP53 mutation status, nutlin-3A stabilized p53 by preventing MDM2-mediated p53 degradation in and Reed-Sternberg (HRS) cells of Hodgkin's lymphoma (HL), Results suggest that the MDM2 SNP309 alone affects neither the risk nor the age at onset of BCC., MDM2 SNP309 is not associated with glioblastoma risk, and is not a prognostic factor., LMP1 of Human herpesvirus 4 augments MDM2 protein expression in a dose-dependent level and leads to a drastic accumulation of ubiquitinated MDM2 species. This effect is associated with the stability of MDM2 modulated by LMP1., Nutlin-3 abrogates both pre-osteoclastic proliferation and differentiation through a p53-dependent pathway, the MDM2 and MDMX complex has a role in abundance and activity of p53, analysis of the p53-Mdm2 feedback loop using protein lysate microarrays, In lung cancer patients, p53 accumulation could be due to a decrease in full-length MDM2 isoform together with an increase of the 57-kDa MDM2 isoform that was unable to stimulate p53 degradation., Rhabdomyosarcoma cells overexpressing MDM2 abrogated ceramide-mediated p21(Cip1/Waf1) induction, G(2) arrest and the late ensuing apoptosis., Single nucleotide polymorphisms are an independent adverse prognostic factor for survival in renal cell carcinoma., P53 Arg72Pro and MDM2 T309G polymorphisms contribute to the risk of developing stomach cancer., damage-activated switch in Hdm2 ubiquitin ligase preference from P53 to itself and Hdmx is central to P53 activation, overexpression of Mdm2 caused by overexpression of SUMO-1 may be involved in tumor aggressiveness even in patients with early stage oral squamous cell carcinoma, MDM2 overexpression is not related to decreased survival length in women operated on for advanced-stage EC., Arrestin in all conformations binds JNK3 comparably, whereas Mdm2 preferentially binds cone arrestin 'frozen' in the basal state., The up-regulation of PTEN inhibited Akt and MDM2, which enhanced the level of p53, thereby inducing G(2)/M arrest and apoptosis., the WNV capsid (WNVCp) is capable of binding to and sequestering HDM2 into the nucleolus., HCMV uses a shift from p53 to HDM2 ubiquitination and destabilization to obtain protracted high levels of p53, while promoting cell cycle traverse, Deficiencies in the function of core DNA replication machinery (e.g., transgenic Mdm2) that are compatible with development and survival nonetheless result in a chronic phenotype leading to stem cell deficiency in multiple tissues and cancer., The results indicate protective associations of p53 Arg72Pro heterozygous variant with postmenopausal and MDM-2 SNP309G along with p53 Arg72Pro heterozygous variant with premenopausal breast cancer risk., Activation of AKT, possibly through the PI3K-AKT pathway, is an important component of ASCC tumorigenesis that contributes to MDM2 and TP53 accumulation in the nucleus., SNP309 of MDM2 alone has little or no effect on the risk of common cancers, but it might modify the time of tumor onset and prognosis, The apoptosis of DNA-damage-induced p53 is reduced in Igf-1r(-/-) mouse embryonic fibroblasts or tumor cells treated with the IGF-1R inhibitor. Furthermore inhibition of IGF-1R reduces p53 and Mdm2 translation through a gene-specific mechanism, ATP binding function of MDM2 can mediate its chaperone function toward the p53 tumor suppressor, CSN5 is a pivotal regulator for both p53 and MDM2, In conclusion, we recommend that the evaluation of MDM2-CDK4 amplification using FISH or Q-PCR be used to supplement IHC analysis when diagnosis of adipose tissue tumors is not possible based on clinical and histologic information alone., this large collaborative study did not find an association of MDM2 SNP309 and TP53 R72P, separately or in interaction, with breast cancer, This is an overview/review of the p53-proto-oncogene protein MDM2 module and its associated pathways from a systems biology perspective. In normal cells, MDM2 negatively regulates the activity of p53., Wip1 acts as a gatekeeper in the Mdm2-p53 regulatory loop by stabilizing Mdm2 and promoting Mdm2-mediated proteolysis of p53., Expression of MDM2 in rhabdomyosarcoma cells transcriptionally repressed p65RelA and suppressed NFkappaB activity, resulting in a reduced growth rate and enhanced apoptosis., MDM2 levels were significantly lower in temporal lobe epilepsy patient brains, a strong gene-smoking interaction was observed between the MDM2 SNP309 and nonsmall cell lung cancer risk, Mutation of the IP6-binding sites impair oligomerization, reduce interaction with Mdm2, and inhibit p53-dependent antiproliferative effects of beta-arr2, SNP309 MDM2 may not be a risk factor for cervical cancer., MDM2 SNP309 accelerates breast and ovarian carcinogenesis in BRCA1 and BRCA2 carriers of Jewish-Ashkenazi descent., Report mdm2 expression in abberant crypt foci and colorectal neoplasms., MDM2 SNP309 serves as a low-penetrance susceptibility tumor marker, 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., Mdm2 is a sensitive biomarker for certain types of genotoxicity., A novel role for the HDM2 oncoprotein in the regulation of angiogenic factors in renal cell carcinoma., High p53 expression level with low MDM2 and p14 ARF levels may be the characteristic features of low differentiated endometrial carcinoma., There is a novel pathway in cell growth and tumorigenesis through negative regulation of FOXO3a by RAS-ERK and MDM2., MDM2 was amplified and overexpressed in well-differentiated and dedifferentiated liposarcomas, Data report the crystal structure of the MDM2/MDMX RING domain heterodimer and map residues required for functional interaction with the E2 (UbcH5b)., These results indicate that in thyroid cancer cells, TAp73alpha is able to increase p53 protein level and function by interfering with Mdm2-mediated p53 degradation., SS18-SSX1 can negatively regulate p53 tumor-suppressive function by increasing the stability of its negative regulator HDM2., Endogenous Mdm2 does not regulate its own stability by self-ubiquitination., MDM2 SNP309, alone or in combination with TP53 R72P, was not associated with oligodendroglial tumors., Study found that Tip60 is capable of selectively inhibiting the Mdm2-mediated conjugation of Nedd8 to p53, whereas it did not affect p53 ubiquitination; hence, the two different E3 ligase activities of Mdm2 can be regulated individually., High-level amplification of MDM2 at 12q13-15 was observed in 4/7 cases of liposarcoma., Although the MDM2 SNP309 G allele is a risk factor for breast cancer, it does not accelerate, but delays the onset of the sporadic disease in Chinese women., CARF exerts a vital control on the p53-HDM2-p21WAF1 pathway that is frequently altered in cancer cells., the MDM2 SNP309G allele was associated with reduced risk of leukaemia. No other association was found between SNP309 and other parameters in both males and females. Thus, the data highlights ethnic differences in the effects of this SNP on cancer risk., The prevalence of MDM2 gene amplifications and single nucleotide polymorphism 309 in 284 colorectal tumors in relation to TP53 mutational status and genomic instability, is analyzed., PKC epsilon mediates TRAIL resistance by Akt-mediated phosphorylation of Hdm2 resulting in suppression of p53 expression and downregulation of Bid in breast cancer cells, isosilybin B treatment enhances the formation of complex between Akt, Mdm2 and AR, which promotes phosphorylation-dependent AR ubiquitination and its degradation by proteasome, Rb antagonizes gankyrin to inhibit MDM2-mediate p53 ubiquitination in cancer cells and suggest that the status of both p53 and Rb is important for efficacy of cancer chemotherapy., Our findings suggested that the T309G polymorphism of Mdm2 was not associated with an increased risk for gastric cancer in Korean population., In stage III non-small cell lung cancer, there was a significant association between TTF-1 and Mdm2, stabilization of MDMX by Akt may be an alternative mechanism by which Akt up-regulates MDM2 protein levels and exerts its oncogenic effects on p53 in tumor cells, Smo mutants augment p53 binding to the E3 ubiquitin-protein ligase Mdm2 and promote p53 ubiquitination., Neither germline variants in p53 nor MDM2 SNP309 play an underlying role in the development of very early onset CRC, CARPs together with MDM2 enhance p53 degradation, thereby inhibiting p53-mediated cell death., MDM2 single-nucleotide polymorphism is associated with the early development of hepatocellular carcinoma in Korean patients with chronic HBV infection., MDM2 SNP309 was not associated with susceptibility to or age of onset of OSCC or OSF. The MDM2 SNP G/G polymorphism was associated with poor OS in advanced OSCC, and the OS and DSF of irradiated patients., These results suggest that a p53-dependent cell cycle checkpoint monitors changes of cellular NS levels via the impediment of MDM2 function., an interactive effect was detected such that MDM2 TT TP53 Arg/Arg double homozygotes, and individuals carrying both a MDM2 G allele and a TP53 Pro allele, were at increased risk of t-AML, Our results indicate that the MDM2 SNP309 is not significantly associated with lung carcinogenesis but point towards gender-specific differences., DLBCL in pre-menopausal women of central European Caucasian ethnicity was not associated with SNP309 G. Neither SNP309 nor SNP72 seem to be correlated with age of onset, diagnosis, or survival of diffuse large B-cell non-Hodgin lymphoma patients., MDM2 regulates dihydrofolate reductase activity through monoubiquitination., MDM2 SNP309 G allele was significantly associated with favorable outcome in female patients, but not in male patients with glioblastomas, Pim-1 induces the p53 pathway in cultured cells and correlate with increased Mdm2 in mantle cell lymphoma, The MDM2 SNP309 genotype influencing MDM2 expression levels was identified as an additional independent risk factor in B-CLL., NFBD1 directly interacts with MDM2 and increases its stability., bronchial squamous cell carcinoma showed increased MDM2 (Murine double minute clone 2) staining at mild dysplasia., an interaction between MDM2 SNP 309 and p53 with respect to tumor behaviors (including disease onset, tumor differentiation, LNECS and disease-free survival) was observed in sporadic Taiwanese OSCCs., TIP60 and p73beta through MDM2 in the transcriptional regulation of cellular apoptosis, MDM2 amplification was observed in a small portion of pleomorphic sarcomas and high-grade sarcomas other than dedifferentiated liposarcomas., Modulation of HDM2 expression could play an important role in tumor angiogenesis and the metastatic process via transcriptional regulation of VEGF., the MDM2 -309 T/G promoter single nucleotide polymorphism has no influence on disease characteristics in chronic lymphocytic leukemia, the MDM2 G/G and T/G-SNP309 alleles are markers of increased predisposition to tumor development and disease aggressiveness in neuroblastoma, the novel MDM2 promoter C1797G polymorphism may be a marker for genetic susceptibility to bladder cancer in Chinese populations, Elevated MDM2 boosts the apoptotic activity of p53-MDM2 binding inhibitors by facilitating MDMX degradation., data clearly show neither association between SNP309 and cancer risk, nor the responsibility of G allele for increased MDM2 or decreased of p53 protein levels in human primary breast tumors., interaction of PI3K/Akt/mTOR and p53 pathways after their simultaneous blockade using the dual PI3K/mTOR inhibitor PI-103 and the Mdm2 inhibitor Nutlin-3., CK2 is tightly associated with TAFII250 and is the principal activity responsible for TAFII250-mediated phosphorylation of Mdm2., The Mdm2 allele may be associated with longer length of stay. However, it does not appear to influence any other clinical characteristics, nor can it be used to predict clinical outcome in sepsis, The G allele of the MDM2 -309T/G polymorphism is associated with 2- to 3-fold increase risk and progression of pancreatic adenocarcinoma and a corresponding decrease in survival., RASSF1A associates with MDM2 and death-domain-associated protein (DAXX) in the nucleus, thereby disrupting the interactions between MDM2, DAXX, and the deubiquitinase, HAUSP, and enhancing the self-ubiquitin ligase activity of MDM2., An MDM2 protein down-regulates the p53 pathway. Recently, an important SNP was discovered in the MDM2 promoter region, which could affect the tumorigenesis of HNSCC by attenuation of the p53 pathway., Report relationship of Ki67, TP53, MDM-2 and BCL-2 expressions with WHO 1973 and WHO/ISUP grades, tumor category and overall patient survival in urothelial tumors of the bladder., MDM2 SNP309 and p53 Arg72Pro polymorphisms might influence the clinical outcome of transitional cell carcinoma of the bladder (TCCB) in a distinctive way between superficial TCCB and invasive TCCB., This first study of the Mdm2 SNP309 in prostate cancer patients suggests no correlation between a certain allelic variant and an increased cancer risk., NIAM is a nuclear interactor of ARF and Mdm2, data are consistent with a model in which Hdmx attenuates p53-dependent activation of the intrinsic apoptotic pathway, and that this occurs upstream of Bax activation, We observed a significant inverse association between MDM2 expression and tumor invasion.Furthermore, the presence of liver metastasis was also significantly associated with low MDM2 expression., Ubiquitin over-expression promotes the destabilization of the ubiquitin protein ligase E6AP, by a mechanism involving self-ubiquitination, and the stabilization of p53., c-Cbl is a new ligase for insulin-like growth factor-I receptor with distinct roles from Mdm2 in receptor ubiquitination and endocytosis, These results indicate that acidic domain of MDM2 provides essential information for acetyltransferase p300 and deacetylase HDAC1 and is indispensable for MDM2 to negatively regulate the acetylation of p53., Overexpression of MDM2 and MDM4 is not a necessary step in retinoblastoma development., Mdm2 induces mono-ubiquitination of FOXO4, hdmX mRNA levels are kept low following genotoxic stress, Accelerated DNA repair required both the NBS1 protein and Hdm2, accompanied by phosphorylation of Hdm2, dissociation of NBS-1 and Hdm2, inhibition of NBS-1 degradation, and accelerated phosphorylation of ATM., MDM2 snp309 as predictor for sensitivity of B-CLL cells to the MDM2 inhibitor nutlin-3a., inhibition of E2F1 by MDM2 was stimulated by ATP & mutation of the ATP-binding domain of MDM2 (K454A) prevented ATP-stimulated inhibition of E2F1; data support a role for the ATP-binding domain in altering the protein-protein interaction function of MDM2, STX6 can be induced by DNA damage and Mdm2 inhibitor Nutlin-3 in a p53-dependent manner., findings indicate that elevated MDM2 mRNA levels in tumours with MDM2 amplification are preferentially driven by the P1 promoter and that the P2 promoter is not only regulated by p53 but also by other transcription factor(s), there was no association between the MDM2 (Mdm2 p53 binding protein homolog)T309G polymorphism and susceptibility or course of disease in patients with Wegeners granulomatosis, results suggest that MDM2 SNP309 does not confer increased risk to oral cancer (OR=1.55, 95% CI=0.77-3.11), however, the GG/TG genotype was associated with later disease onset in women above 55 years of age., These studies provide the first insights into the molecular basis through which Arf nullifies the p53-inhibiting activity of Hdm2, indirectly activating the tumor-suppressor function of p53 in mammalian cells., These results provide evidence for the potential involvement of MDM2 SNP309 in pigmentary traits., the presence of conserved and non-conserved interactions along the conformational transition pathway that may be exploited in the design of selective and dual modulators of MDM2 activity, SNP309G/G is associated with poor prognostic breast cancer features in the Scottish population; a novel SNP, SNP285, that is in linkage disequilibrium with SNP309, may also have a role in breast tumorigenesis, No evident association between SNP309 and event free survival was found. The lack of association between SNP309 and MYCN status indicates that MDM2 SNP309 may be a new independent prognostic factor for stage 4 NB., Increased MDM2 expression and/or MDM2 amplification can be employed to aid discrimination of inflammatory well-differentiated liposarcoma from fibroinflammatory mimics, The levels of HDM2 transcripts originating from the constitutive P1 and p53-sensitive P2 promoter in 133 soft tissue sarcomas was correlated the results with the age of diagnosis and the patients' outcome., Mdm2 regulates p53 levels also by targeting ribosomal protein L26 for polyubiquitylation and proteasomal degradation., Genetic polymorphism in MDM2 may be associated with susceptibility to colorectal cancer in a Chinese population., Although the MDM2 SNP309 does not portend decreased survival, the increased incidence of the mutant G allele in patients with glioblastoma multiforme (GBM) suggests a potential role in the molecular pathogenesis of GBM., Polymorphisms in the MDM2 gene is associated with significantly poorer response to treatment in pancreatic cancer patients., demonstrated no evidence for association of MDM2 SNP 309 or TP53 Arg72Pro allelic variants alone, or in combination, with overall survival (Figure 1A), progression free survival, relapse free survival or time to transformation, Hdm2 is expressed in pancreatic cancer cells as a result of activated Ras signaling, and regulates cellular proliferation and the expression of target genes by p53-independent mechanisms., nucleoplasmic relocation of nucleostemin during nucleolar disassembly safeguards the G2-M transit and survival of continuously dividing cells by MDM2 stabilization and p53 inhibition., PI3K/Akt/mdm2 signalling pathway can be activated by doxorubicin and suppress apoptosis by promoting phosphorylation of mdm2 in a gastric cancer cell line., neither the TP53 Arg72Pro polymorphism nor the MDM2 SNP309 contributes significantly to either susceptibility or disease severity in systemic lupus erythematosus, c-Abl not only targets Hdm2, but also Hdmx, which together contribute to p53 activation in response to DNA damage., results support the hypothesis that p53 function is suppressed by aberrant HDM2 activity and suggest the possibility of targeting the p53-HDM2 regulatory axis as a therapeutic strategy in synovial sarcoma, All cases also tested positive for the MDM2 protein, but with varying degrees of nuclear expression and a predominance of slightly stained cells., p53 is selectively stabilized because the unanchored polyubiquitin that accumulates after USP5 knockdown is able to compete with ubiquitinated p53 but not with Mdm2 for proteasomal recognition, RYBP interacts with MDM2 & decreases MDM2-mediated p53 ubiquitination. The RYBP-binding domain of MDM2 was mapped to residues 180-298., p53-Mdm2 protein-protein and p53 mRNA-Mdm2 interactions affect Mdm2-mediated control of p53 expression using the Phe19Ala p53 mutant., Data suggest that overexpression of Akt1 and Mdm2 may be related to esophageal carcinogenesis, and that Akt expression regulates Mdm2 expression, which may in turn regulate the function of wild-type p53., The authors report that MDM2, known as an E3 ligase for p53, is a novel E3 ligase for Vif and induces polyubiquitination and degradation of Vif., MDM2 SNP309 genotype is associated with the risk of breast cancer and an earlier age of onset in Taiwanese women., The authors found that liberation of p53 through chemical antagonism of one of its major ubiquitin ligases, MDM2, using the small-molecule Nutlin-3 led to apoptosis of established LCLs and suppressed EBV-mediated transformation of primary B cells., The physical interaction between PML3 and TIP60 protects TIP60 from Mdm2-mediated degradation, suggesting that PML3 competes with MDM2 for binding to TIP60., Mdm2-mediated control of p53 synthesis and degradation has evolved in the p53 mRNA sequence and its encoded amino acids., 14-3-3 proteins bind to Pim kinase-phosphorylated Ser166 and Ser186 on the human Mdm2, but not to protein kinase B/Akt-phosphorylated Ser166 and Ser186., Results suggest that Mdm2 and PCAF may function as part of a multi-subunit E3 complex in their regulation of Chk2 turnover., the RING finger domain has a role in the allosteric control of MDM2 conformation and activity, The combination of the MDM2 SNP309 and the three TP53 polymorphisms appear to be related to a higher grade of endometrial cancer., Analysis of pair wise genotype combinations revealed increase in risk for specific p73-MDM2 and p73-p53 genotype combinations., current understanding on p53 ubiquitination by Mdm2 with a particular focus on how the balance between protein levels and other post-translational modifications will direct the p53 response (Review), Ubiquitination of mammalian AP endonuclease (APE1) regulated by the p53-MDM2 signaling pathway., MDM2SNP309G/G main effect on BRCA1/2 positive mutation carriers is linked to its effect on patients survival., Our findings suggest that the MDM2 309T>G polymorphism is an important modulator of hepatocellular carcinoma development in Moroccan patients., EBNA3C enhances the intrinsic ubiquitin ligase activity of Mdm2 toward p53, which in turn facilitated p53 ubiquitination and degradation, The MDM2 SNP309 G/G genotype may be a genetic risk factor for missed abortion, Hdm2 protein is a ku autoantigen ibiquitin ligase and that Proto-Oncogene Proteins c-akt inhibits Bax-mediated apoptosis by maintaining Ku autoantigen levels through the promotion of Hdm2 protein nuclear translocation., MDM2 released from p53 by RITA promotes degradation of p21 and the p53 cofactor hnRNP K, required for p21 transcription, These findings deciphered the structural basis for high-affinity peptide inhibition of p53 interactions with MDM2 and MDMX., This meta-analysis suggests that the MDM2 309G allele is a low-penetrant risk factor for developing lung cancer in Asians., ALK signaling leads to the functional inactivation and/or degradation of p53 in JNK and MDM2 dependent manners., Gankyrin downregulates p53 expression and not Mdm2 expression in a zebrafish model., Results highlight the role of SMAR1 in masking the active phosphorylation site of p53, enabling the deacetylation of p53 by HDAC1-MDM2 complex, thereby regulating the p53 transcriptional response during stress rescue., Crystal structures of two complexes, a p53-like mutant peptide with the N-terminal domains of Mdm2 and Mdmx, respectively, are presented., Results suggest that MDM2 may play an important role in the development of melanoma in women, Nucleostemin is a target for Mdm2-mediated ubiquitination and degradation when not bound to GTP., MDM2 acts as an ubiquitin E3 ligase, downstream of p53, to regulate the degradation of mammalian FOXO factors., Findings confirmed the relationship of p53, MDM2, and COX-2 with the biological process of pancreatic cancer., The binding interactions between the N-terminal transactivation domain (TAD) of p53, the TAZ1, TAZ2, KIX, and nuclear receptor coactivator binding domains of CBP, and the p53-binding domain of HDM2, are examined., USP33 and Mdm2 function reciprocally and favor respectively the stability or lability of the receptor beta-arrestin complex, a beta-arrestin-scaffolded pool of the E3-ubiquitin ligase, Mdm2, mediates PDE4D5 ubiquitination, murine double-minute 2 homolog single nucleotide polymorphism 309 (MDM2-SNP309) has been reported to profoundly accelerate tumor formation, suggesting that it may also represent a powerful gynecologic cancer predisposing allele., MDM2 T309G G/G was associated with squamous cell carcinoma., Upregulation of XIAP in MDM2-overexpressing cancer cells in response to irradiation resulted in resistance of these cells to radiation-induced apoptosis, When the p53 and MDM2 polymorphisms were combined, no multiplicative joint effect between the MDM2 GG and p53 Pro/Pro genotypes exists in the risk of developing AML, Data show that it can function in an autoregulatory loop consisting of RAP80, HDM2, and the p53 master regulatory network, implpying an important role for this loop in genome stability and oncogenesis., Results indicate that wtp53 and p53 mutants may differentially control cancer invasion and metastasis through the p53-MDM2-Slug pathway., Study provides evidence supporting the association of MDM2 SNP309 with high-grade osteosarcoma risk in females and shows that TP53 Arg72Pro has a prognostic value for overall survival and EFS in osteosarcoma patients., SNP genotyping of a sclerosing rhabdomyosarcoma reveals high aneuploid profile and a specific MDM2 amplification., results suggest that the single nucleotide polymorphism G309 in the Mdm2 promoter might be an important genetic predisposing factor, and possibly indicate a molecular mechanism of disease regarding malignant melanoma, No association was found between the the MDM2-SNP309) variant and earlier age of onset of Li-Fraumeni syndrome, Combined MDM2 and Ki-67 expression levels could be considered for risk stratification of patients with prostate cancer in clinical trials., Changes in the p53, MDM2, and p14(ARF) protein levels were not correlated with 5-year survival rate of esophageal squamous cell carcinoma., meta-analysis supports the view that MDM2(mouse double minute 2 ) SNP309 gene is a low-penetrance susceptible gene in the development of lung cancer, and the relationship of MDM2 SNP309 and lung cancer is stronger for never smokers., AP-4 participates in a transcriptional-regulating complex at the HDM2-P2 promoter in response to DNA damage., analysis of different p53 recognition of MDM2 and MDMX, The MDM2 SNP309G allele significantly decreased the risk of epithelial ovarian cancer and might be a potentially protective factor for EOC development in Chinese women., Accelerated decline in lung function in cigarette smokers is associated with MDM2 polymorphisms., MDM2 SNP309 polymorphism is not associated with prostate cancer., Study shows that human cone precursors prominently express MDM2 and N-Myc, that retinoblastoma cells require both of these proteins for proliferation and survival, and that MDM2 is needed to suppress ARF-induced apoptosis in cultured retinoblastoma cells., MDM2 SNP309 status does not affect the risk of developing neuroblastoma nor disease outcome for localized cancer cases, it significantly correlates with survival in stage 4 neuroblastoma patients., 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., both NOLC1 and tumor protein 53 work together synergistically to activate the MDM2 promoter in NPC cells., Effect of TP53 PEX4 and MDM2 SNP309 on age at diagnosis was similar to the one reported in other series and was smaller than the one of TP53 PIN3 (TP53 PIN3, Report therapeutic potential of Mdm2 inhibition for the treatment of patients suffering from high-risk nonseminomatous testicular germ cell tumors with wild-type p53 status., Results define translational regulation of MDM2 expression by eIF4E and provide a molecular mechanism underlying rapamycin-induced p53-dependent apoptosis., no association existed between any particular MDM2 SNP309 genotype, overall survival and time to treatment in chronic lymphocytic leukemia, Stochastic modeling and simulation of the p53-MDM2/MDMX loop., MDM2 SNP309 represents a risk factor for breast cancer in Chinese women but not in non-Chinese women, Genetic variants in p14ARF, alone or in combination with MDM2 Del1518 polymorphism, contribute to the development of chronic benzene poisoning in occupational exposure to benzene in a Chinese population., HDM2 protein functions as a HEXIM1 protein -specific E3 ubiquitin ligase., Results suggest that alteration of the substrate specificity via binding to Mdmx may contribute to efficient ubiquitination and inactivation of p53 by Mdm2., conserved intronic sequences in intron 11 of MDM2 are required for normal splicing, Polymorphisms in p53 codon 72 and MDM2 SNP309 may be implicated in breast cancer of young women., Data show that nutlin-3 activates p53 resulting in a dramatic increase in MDM2 expression and a marked reduction in total Rb protein levels., we provided evidence for a crucial role for direct inhibition of p53 by MDM2 and suppression of the p19(ARF)/p53 axis in neuroblastoma tumorigenesis, DNA pull-down assays using a 7,8-dihydro-8-oxoguanine duplex oligonucleotide as a substrate found that RPS3 acted as a scaffold for the additional binding, zinc deficiency differentially modulated the Akt-Mdm2-p53 signaling axis in normal prostate cells vs. the Akt-p21 signaling axis in malignant prostate cells., These data propose a novel mechanism by which MDM2 controls the cell cycle in normal cells and how cancer cells may escape this important safety barrier., Strong MDM2 and pAKT, variable P53 and null P21 expressions were associated with adenoid cystic carcinoma., The interplays among HIF-1alpha and Hdm2 and HIF1 could be potential targets for treating tumors overexpressing HIF-1alpha., There was no evidence that TP53 Arg72Pro or MDM2 309T>G, either singly or in combination, influence breast cancer risk in BRCA1 or BRCA2 mutation carriers., Genetic variation in MDM2 promoter is associated with gastric cancer susceptibility in Chinese patients., Observations suggest a novel role of the MDM2 SNP309 locus in regulating PDAC tumor formation in a male-specific manner., We demonstrate that Sgk1 activates MDM2-dependent p53 ubiquitylation., CK1alpha plays a central role in mediating MDM2 control of p53 and E2F-1 protein stability, the TP53 and MDM2 genotypes might be useful prognostic factors following CRT in bladder cancer., The function of MDM2 depends on the p53 P72R genotype, resulting in either an increased or reduced risk for rheumatoid arthritis., SAPHO syndrome may be linked to an imbalance between MDM2 and p53 regulation with a "weak" p53-response associated with the Mdm2 SNP 309 G allele., Data show that the stability of MDM2 is regulated by NEDD8 pathway and identify NEDP1 that deneddylates MDM2, resulting in MDM2 destabilization concomitant with p53 activation., The expressions of mdm2 and p53 are closely related with the pathogenesis and progression of nasal NK/T-cell lymphoma., High-risk HPV types may be associated with oral carcinoma, by cell-cycle control dysregulation, contributing to oral carcinogenesis and the overexpression of mdm2, p27 and cathepsin B., ATM controls p53 stability by regulating MDM2 RING domain oligomerization and E3 ligase processivity, Study identified an overrepresentation of focal amplifications of known (FGFR3, CCND1, MYC, MDM2) and novel candidate genes (MYBL2, YWHAB and SDC4) in stage Ta bladder carcinoma., Data show that the PLK1 phosphorylates MDM2 at Ser260 and stimulates MDM2-mediated turnover of p53., MDM2 SNP309 did not show any association with primary susceptibility to childhood ALL., Data show that ectopic expression of wild-type USP2a but not a catalytic mutant prevents Mdm2-mediated degradation of MdmX., These data provide a possible mechanism on how p53 regulate HBx stability and also a new clue for the study of p53 mutation and hepatocellular carcinoma development., DHCR24 is elevated in response to HCV infection and inhibits the p53 stress response by stimulating the accumulation of the MDM2-p53 complex in the cytoplasm and by inhibiting the acetylation of p53 in the nucleus., Polymorphism of MDM2 promoter 309 may increase the risk of endometrial cancer., the Hdm2/p53 and proteasome pathways have a role in enhancing the antitumor activity of bortezomib, MDM2-SNP309 GG genotype may not have a significant role in hepatocellular carcinoma in the Taiwanese population, except in patients infected by hepatitis virus, Lower MDM2 promoter containing the SNP309 GG genotype was associated with p53-null lung cancer., By following the interaction of the two entire proteins by atomic force spectroscopy, results have assessed the formation of a specific complex between p53 and Mdm2., Measurement of MDM-2 as a bad prognostic marker even in cases with non-mutant p53 is very important. Moreover, MDM-2 may be a potential molecular target for production of new cancer therapy., RL-3, like PRL-1, can negatively regulate p53 via the activation of PIRH2 and MDM2 in cancer cells., In tumor cells where both Hdm2 and HdmX are overexpressed, removal of one leads to an anti-proliferative effect in cells harboring wild-type p53 and induction of p53 cell cycle arrest genes that negatively feedback onto the E2F pathway., TGF-beta1-induced expression of human Mdm2 correlates with late-stage metastatic breast cancer., Under normal conditions, nuclear and not cytoplasmic DYRK2 is ubiquitinated by MDM2, resulting in its constitutive degradation. In the presence of proteasome inhibitors, we detected a stable complex of DYRK2 with MDM2 at the nucleus., An interaction between MDM2 and iron in the pathogenesis of hepatocarcinoma., Breast cancer homozygous carriers of the G-allele in MDM2 had worse survival only within the group of TP53 C-allele carriers., The proteins p53, p21/WAF1, and MDM2 were overexpressed in all the hepatocellular carcinoma cases in this study., find significant levels of HDM-2 in the membranes of a variety of cancer cells but not in the membranes of several untransformed cell lines, The p53-Mdm2 interaction and its regulation have been conserved from a basal eumetazoan since the pre-cambrian era over 1 billion years ago., B-CLL cells of patients with the MDM2 SNP309 GG genotype had significantly lower miR-34a expression levels compared with patients with the TT genotype., MDM2 amplification in 3 cases, all at diagnosis and relapse and p14(ARF) inactivation in 12 of 41 (29%) cases, These results reveal Mdm2 and Hausp as important regulators for Daxx functions by controlling Daxx ubiquitination and stability., Studies indicate that both Mdm2 and Mdmx receive input from numerous signaling pathways and interact with many proteins in addition to p53., Study identifies RFWD3 as a positive regulator of p53 stability when the G(1) cell cycle checkpoint is activated and provides an explanation for how p53 is protected from degradation in the presence of high levels of Mdm2., Molecular dynamics simulations have been used to explore the differences in binding of p53 and nutlin to MDM2/MDMX., Quantitative real-time PCR of MDM2, CDK4, and 25 other genes in osteosarcoma tumors showed that this region contains two different amplicons, We found no association between MDM2 SNP309 and cervical cancer, The mean RNA expression level of p53 and that of hdm2 were elevated in large-sized, poorly differentiated, node-positive ductal breast carcinomas, MDM2 SNP309 TT rather than the GG genotype is associated with increased risk of lung cancer in a population of non-smoking Chinese women in Singapore, association between MDM2 SNP309 and both ferritin and LDH in patients with stage 4 neuroblastoma disease, MDM-2 is overexpressed in a significant number of childhood acute lymphoblastic leukemia, it is more frequent in relapsed cases and its frequency is not related to p53 status., MDM2 promotes proteasomal degradation of p21Waf1 via a conformation change, MDM2, MDMX, Pirh2 and COP1 might inhibit p53 activity synergistically in vivo., The role of the allelic variants in ARLTS1, RAD51 and MDM2 acting in the tumor suppressor, DNA repair and p53 pathways as risk factors for familial breast cancer in 147 patients displaying characteristics of familial disease, was investigated., Show in pancreatic cancer the growth inhibition and apoptosis by novel MDM2 inhibitors (MI-319 & 219) through reactivation of p53 pathway., Findings suggest that MDM2 and MDMX are responsible for the functional inactivation of p53 in testicular germ cell tumors., p16INK4A hypermethylation is associated with accumulation of MDM2 in esophageal squamous cell carcinoma development., The findings suggest that polymorphisms of MDM2 and TP53 genes may be genetic modifier for developing nasopharyngeal carcinoma., The presence of MDM2/CPM amplification in the pleomorphic liposarcoma (PL) component of mixed well-differentiated liposarcoma (WDL)/PL suggests that a subset of PL may arise through tumor progression of WDL, This study reveals that mTORC2 is a critical target of PLD-mediated survival signals and identifies SGK1 as a downstream target of mTORC2 for the stabilization of HDM2., MDM2 promoter single nucleotide polymorphism 309 G allele is associated with hepatocellular carcinoma., In U2OS cells, depletion of Hdm2 or addition of the Hdm2-resistant hTERT mutant strengthened the cellular protective effects against apoptosis, propose that Mdm2 facilitates, or at least enhances, the association of p53 with the proteasome and that phosphorylation of the central domain of Mdm2 regulates this process, In this report, with a high proportion of B-CLL patients with an advanced Binet stage and with an unmutated IgVH gene, MDM2 SNP309 was found to be independently associated with overall survival ., the MDM2 309 G allele probably acts as a colorectal cancer risk factor, especially in Asians, A multiplicative joint effect of MDM2 and p53 codon72 polymorphism on risk, was observed. The MDM4 polymorphism had no significant effects., Mdm2 is a major negative regulator of the tumor suppressor p53 and has long been thought to inhibit p53 in two ways., Single nucleotide polymorphism 309 GG within MDM2 gene is associated with cutaneous melanoma Breslow thickness., MDM2-SNP309 (T/G) and high-risk HPV infection may be closely associated with cervical carcinogenesis in a Japanese population., A fraction of mitochondrial Hep27 translocates to the nucleus, where it binds to Mdm2 in the central domain, resulting in the attenuation of Mdm2-mediated p53 degradation., Knockdown of L29 or L30 enhanced the interaction of MDM2 with L11 and L5 and markedly inhibited MDM2-mediated p53 ubiquitination, suggesting that direct perturbation of 60 S ribosomal biogenesis activates p53 via L11- and L5-mediated MDM2 suppression., p53 was overexpressed in cells lacking Mdm2 and p53, p53 levels were unaffected by anoikis conditions, The variant SNP 309 influences susceptibility to pediatric AML, but does not impact overall response to therapy., Pathogenesis of both oral verrucous carcinoma and hyperplasia may be at least partially attributed to the overexpression of MDM2 protein and moderate expression of HSP 70 protein in both lesions., histone methyltransferases SUV39H1 and EHMT1 bind specifically to MDM2 but not to its homolog MDMX., S100A1, S100A2, S100A4, S100A6 and S100B interacted with MDM2 (2-125)., results may indicate that the HDM2-related resistance to chemotherapeutic drugs of neuroblastoma is regulated by p53/p73-dependent Noxa expression in neuroblastoma., SCYL1-BP1 can be ubiquitinated and degraded by Pirh2 but not by MDM2, which suggests that SCYL1-BP1 can be regulated by Pirh2., MDM2 and CDK4 immunostains therefore reliably distinguish low-grade osteosarcoma from benign histological mimics, The loss of FHIT and over-expression of MDM2 may play an important role in the carcinogenesis of oral submucous fibrosis., The Mdm2-p53 interaction is decreased upon deletion, mutation or acetylation of the p53 C terminus., By searching for the kinases responsible for Mdm2 S163 phosphorylation under genotoxic stress, the authors identified S6K1 as a multifaceted regulator of Mdm2., Dada demonstrate that HDMX-L cooperates with HDM2 to promote the ubiquitination of p53 and that p53-induced HDMX transcription from the P2 promoter can play a key role in the attenuation phase of the p53 response., Histone deacetylase inhibitors enhance the anticancer activity of nutlin-3 and induce p53 hyperacetylation and downregulation of MDM2 and MDM4 gene expression., results provide insight into the signaling pathways controlling Mdm2 destruction and further suggest that compromised regulation of Mdm2 results in attenuated p53 activity, thereby facilitating tumor progression, The authors showed that USP7 N-terminal domain recognized two of six P/AxxS motifs of HdmX ((8)AQCS(11) and (398)AHSS(401)) and also identified an additional interaction site ((397)PSTS(400)) on Hdm2., Data show that ERK8 prevents HDM2-mediated PCNA destruction by inhibiting the association of PCNA with HDM2, and implicate ERK8 in the regulation of genomic stability., Results indicate that the risk of OSCC associated with HPV16 L1 seropositivity is modified by MDM2 promoter polymorphisms., p21 and p53 are recruited to ALT-associated PML-nuclear bodies after Nutlin-3a (MDM2 antagonist) treatment, suggesting that they may play a previously unrecognized role in telomere maintenance, Data indicate that double-minute 2 protein (MDM2) 309GG variant was at reduced risk for developing prostate cancer (CaP)., Data provide causal evidence for increased cancer risk in carriers of the Mdm2(SNP309G) allele., In tumors with wild-type p53, its tumor suppressor function is often impaired by MDM2 overexpression that targets p53 for proteasomal degradation. Likewise, MDM2 targets HIPK2 for protein degradation impairing p53-apoptotic function., Data suggest that SCYL1-BP1 is a novel regulator of the MDM2-p53 feedback loop and that it may be a potential tumor suppressor., Importance of p53 regulators in prostate cancer development and progression., Data show that phosphorylation by p38 triggers an interaction between Rb and the Hdm2, leading to degradation of Rb and cell death., These findings suggest that TP53 and MDM2 polymorphisms play a role in prostate cancer susceptibility in southern Chinese Han population., no evidence of MDM2 amplification in most tumor cells., Studies indicate that mono-ubiquitination of p53 by MDM2 leads to its nuclear export., Data report that depletion of L37 leads to cell cycle arrest in a MDM2/L11- and p53-dependent manner., p53-P72 and p53-R72 induce different levels of MDM-2 transcription, miR-192, 194, and 215, which are downregulated in a subset of newly diagnosed multiple myelomas, can be transcriptionally activated by p53 and then modulate MDM2 expression., Results suggest that the MDM2 SNP309 G allele may act as a susceptibility gene for the development of classic Kaposi's sarcoma in Caucasian patients., a likely mechanistic basis for MDM2-promoted motility, A case-control study in Japan showed that the combination of the TP53 72P and SNP309 G alleles was associated with a moderately increased risk of colorectal cancer., SRF and Enigma coexpressed with MDM2 but not p53 in several liver and stomach tumors., MDM2 protein levels are strongly associated with and regulated by eIF4E in a posttranscriptional mechanism in esophageal cancer., a direct link between genotoxic stress-activated c-Abl kinase signaling and Mdm2-Mdmx complex formation, This comprehensive analysis of the Pirh2 and Mdm2 RING domains provides structural and mechanistic insight into p53 regulation by its E3 ligases., The role of MDM2 in the regulation of not only p53 but also p73 transcription factor, and possibly even p63., These data suggest that expression of p53 and mdm-2 in primary and recurrent mucoepidermoid carcinoma correlates with the high histological grade., MDM2 promotes Itch-mediated degradation of p73 through the interaction with Itch in HeLa cells., Findings suggest that eBP1 p48 functions as an oncogene by promoting glioma tumorigenicity via interactions with HDM2 that contribute to p53 downregulation., The aim of this study was to investigate murine double minute-2 (MDM2) gene copy number changes in colon carcinoma, GNL3L bound MDM2 in vivo, stabilizing MDM2 and preventing its ubiquitylation., study reveals a multilevel interplay between RPS27L/S27 and p53-MDM2 axis, with RPS27L functioning as a p53 target, a MDM2 substrate and a p53 regulator, a mechanism underlying the SENP2-mediated regulation of Mdm2 that is critical for genome integrity in p53-dependent stress responses., A flexible N-terminus "lid" region of MDM2 can regulate p53-MDM2 interactions., novel evidence that the inhibition of Nrf2 can suppress Mdm2 expression, which may result in p53 signaling modulation, small ie, Cyrillicsmall er, Cyrillicsmall sha, Cyrillicsmall yeru, Cyrillic study suggests that MDM2 SNP309 can be considered a risk marker for the development of nasopharyngeal carcinoma mainly in early ages probably as an initiation marker for potential cancer development., MDM2 antagonist nutlin-3 has significant anticancer effects against human hepatocellular carcinoma cells, regardless of p53 status., Single nucleotide polymorphisms in MDM2 gene is associated with non-small cell lung cancer., Pretreatment overexpression of MDM2 protein may contribute to poor initial prednisone therapy response in acute lymphoblastic leukemia., CREB preferentially down-regulates MDM2 and thereby contributing to p53-mediated apoptosis in response to glucose deprivation, analyses showed that the TP53 germ-line mutation and its interaction with gender were strongly associated with familial cancer incidence and that the association between MDM2 SNP309 and increased cancer risk was modest, These results suggest that SMT3IP1 is a new regulator of the p53-Mdm2 pathway., Comparing MDM2 promoter status among different cohorts of ovarian and breast cancer patients versus healthy controls (n = 3646), SNP285C reduced the risk of both ovarian and breast cancer among SNP309G carriers, Loss of beta-TRCP or Casein Kinase I function contributes to elevated Mdm2 expression that is frequently found in various types of tumors., loss of CSN6 enhances p53-mediated tumor suppression in vivo and CSN6 plays an important role in regulating DNA damage-associated apoptosis and tumorigenesis through control of the MDM2-p53 signaling pathway, CDK4, MDM2, and p16 expression in the whorls suggests that they share a similar genetic background to well-differentiated, show that ubiquitination factor E4B (UBE4B), an E3 and E4 ubiquitin ligase, physically interacts with p53 and Hdm2 (also known as Mdm2 in mice). UBE4B promotes p53 polyubiquitination and degradation and inhibits p53-dependent transactivation and apoptosis, Data suggest that irradiation causes RFP2 overexpression, which enhances ionizing radiation-induced apoptosis by increasing p53 stability and decreasing AKT kinase activity through MDM2 and AKT degradation., Immunohistochemical expression of MDM2 and CDK4 is specific and provides sensitive markers for the diagnosis of low-grade osteosarcomas., A secondary role for Nutlin-3 as a DDR triggering agent, independent of p53 status, and unrelated to its role as an MDM2 antagonist., Functional polymorphisms between p53 and HDM2 are associated with missed abortion., The phenotype of MDM2 auto-degradation after DNA damage is due to epitope masking by phosphorylation., the intact E3 ligase activity of Mdm2 is critical for normal subcellular distribution and functions of beta-arrestin2, Report elevated transcript levels from the P1 promoter are associated with poor prognosis in human pancreatic ductal adenocarcinoma., Knockdown of mdm2 expression by its specific small interfering RNA with overexpression of wild type p53 gene offers synergistic inhibition of prostate cancer cell growth in vitro and in vivo., PERP expression stabilizes active p53 via modulation of p53-MDM2 interaction in uveal melanoma cells., an ubiquitination-independent mechanism of p53 regulation by MDM2, Met ensures cell survival through a new path in which c-Abl and p38-MAPK are employed to elicit p53 phosphorylation on Ser(392) and Mdm2 upregulation., defects in effector molecules downstream of p53 are remarkably rare in neuroblastoma, and identify p14(ARF) as a determinant of the outcome of the response to MDM2 inhibition, Ubiquitin ligase parkin promotes Mdm2-arrestin interaction but inhibits arrestin ubiquitination, The gene-gene interaction of MDM2 and TP53 polymorphisms increased breast cancer risk in a multiplicative manner in an ethnic Arab population., Functional inactivation of endogenous MDM2 and CHIP by HSP90 causes aberrant stabilization of mutant p53 in human cancer cells, we investigated whether MDM2-SNP309 is associated with p53 R72P genetic polymorphism for the risk of breast cancer development in Asian Taiwanese., MDM4 might play a role in colorectal carcinogenesis that is not limited to negative regulation of p53 in combination with MDM2, MDM2 interacts with NME2 and suppresses the ability of NME2 to negatively regulate cell motility in renal cancer, CXCR4 is capable of orchestrating a complex alteration in signaling networks, which include upregulation of multiple receptor tyrosine kinases (RTKs), deregulation of p53/MDM2 axis, Data suggest that p53 activation by MDM2 antagonists in combination with androgen depletion may offer an efficacious new approach to prostate cancer therapy., meta-analysis suggested that the GG genotype of MDM2 SNP309 was significantly associated with the increased endometrial cancer risk [review], S27a plays a non-redundant role in mediating p53 activation in response to ribosomal stress via interplaying with MDM2., the MDM2 309 G allele probably acts as an important hepatocellular carcinoma risk factor, MdmX protein is essential for Mdm2 protein-mediated p53 polyubiquitination., elevated Mdm2 expression cooperated with aging to increase the likelihood of gaining certain chromosomal abnormalities of the kind thought to lead to cancer development, Studies indicate that Mdm2 has the ability to catalyze both mono- and poly-ubiquitination of p53., MDM2 309G polymorphisms contribute to the risk of developing chronic lymphocytic leukemia, MDM2 SNP309, A2164G, and p53 codon 72 SNPs may collectively contribute to non-oropharyngeal cancer risk and that MDM2 SNP309 individually or in combination with p53 codon 72 may accelerate the development of non-oropharyngeal cancer in women, A restricted pattern of p53 overexpression is preferentially associated with microsatellite instability high phenotype. Its association with concomitant murine double minute 2 overexpression suggests an alternative mechanism of p53 pathway deregulation., Association of the germline TP53 R72P and MDM2 SNP309 variants with breast cancer survival in specific breast tumor subgroups, SPARC has a cell-autonomous survival activity, which requires Akt-dependent regulation of p53, MDM2 SNP309 and TP53 R72P are significantly associated with severe neutropenia and fibrile neutropenia, respectively, in breast cancer patients treated with FEC100, and their combination may be a useful predictor of severe and fibrile neutropenia., Data indicate that MYCN is a central modulator of the p53/MDM2/p14ARF negative feedback loop., MDM2 SNP309 polymorphism may increase the risk to breast cancer in Asian and African population., Caspase-2 directly cleaves the E3 ubiquitin ligase Mdm2 at Asp 367, leading to loss of the C-terminal RING domain responsible for p53 ubiquitination., Data suggest E3 ligase murine double minute-2 (MDM2) as a drug target in melanoma cells, and identify E2F1 as a biomarker to consider when stratifying putative candidates for clinical studies of p53-MDM2 inhibitors., Increased levels of cAMP augment the binding of p53 to its negative regulator HDM2, overriding the DNA damage-induced dissociation of p53 from HDM2., Coexpression of p53/MDM2 identifies a subset of patients with poor prognosis, despite all of them having organ-confined disease., HDM2 mRNA is frequently mutated by alternative splicing in colorectal cancer, and it may play a role in colorectal tumorigenesis or cancer progression., 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., meta-analysis suggested that the MDM2 SNP309 polymorphism is a low-penetrance risk factor for the development of colorectal cancer, particularly among Asians, data indicate that the JAK2(V617F) mutation affects p53 response to DNA damage through the upregulation of La antigen and accumulation of MDM2, The MDM2 309SNP showed a weak negative association of allele G in heridatary retinobalstoma in Italy., Here, we report that MYCN expression was regulated by the oncoprotein MDM2 at the post-transcriptional level and was associated with neuroblastoma cell growth., Our findings support experimental data implicating combined effects of MDM2 protein and the p53-mediated pathway in breast carcinogenesis., HDM-2 inhibition suppresses expression of ribonucleotide reductase subunit M2, and synergistically enhances gemcitabine-induced cytotoxicity in mantle cell lymphoma., Modulation of MDM2 differentially regulates p53 in neuroblastoma cells with and without MYCN amplification., the data of meta-analysis suggests that MDM2 SNP309 is a potential biomarker for cancer risk, 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., These data suggest that IRTKS is a novel regulator of p53, modulating low level of MDM2-mediated p53 ubiquitination in unstressed cells., The MDM2 oncogene is amplified in a substantial proportion of ER+ early-stage breast carcinomas and an independent parameter for poor patient outcome in this subgroup., MDM2 induces SUMO-3 conjugation of p53., Hydrophilic residues are crucial for ribosomal protein L11 (RPL11) interaction with zinc finger domain of MDM2 and p53 protein activation, Murine double minute 2 showed no difference of expression in any group of tumors, no correlation with p53 expression., It was shown that high level of Ebp1 expression led to enhancee HDM2 phosphorylation by Akt and inhibited the self-ubiquitination of HDM2 by up-regulation of Akt activity., Overexpression of MDM-2 protein may play an important role in glioma tumorigenesis, but may not be involved in glioma progression. The overexpression of MDM-2 protein was an early event in malignant transformation of glioma., MEK-ERK signaling is required for MDM2 expression in stem-like Glioblastoma cells, which prevents p53 activation and subsequent suppression of MGMT expression., this is the first study to show that a variant genotype of p53 Arg72Pro or MDM2 SNP309 may modify the arsenic-related RCC risk even in a non-obvious arsenic exposure area., DNA damage promotes MDM2 phosphorylation near the RING domain and inhibits MDM2 RING domain dimerization., MDM2 plays a p53-independent role in the regulation of vascular endothelial growth factor, which may promote tumor growth and metastasis., The overall results point towards a novel ability of HDM2 in regulating HIF-1alpha and p-STAT3 levels even in normoxic conditions that eventually lead to an up-regulation of VEGF expression., Single nucleotide polymorphisms of CCND2, RAD23B, GRP78, CEP164, MDM2, and ALDH2 genes were significantly associated with development and recurrence of hepatocellular carcinoma in Japanese patients with hepatitis C virus., Analysis of MDM2 SNP 309 in a large cohort of patients with familial myeloproliferative neoplasm did not find an effect of the polymorphism on disease susceptibility, age at disease onset, disease progression, and association with JAK2 (V617F) mutation, High expression of the HDM2 gene is associated with chronic lymphocytic leukemia., Mdm2 physically associates with PolH and promotes PolH polyubiquitination in vivo and in vitro, The studies provide insights on how nucleolar stress through L11 and NEDD8 can activate the transcriptional activity of p53., Mdm2/NEDD8/HuR regulatory framework is essential for the malignant transformation of tumor cells., changes in nucleolin conformation can alter the availabilities of domains in vivo to modulate theoverall impact of nucleolin on Hdm2 activity and hence on p53 stability., Hoiamide D displays inhibitory activity against the p53/MDM2 interaction, A bacterially expressed human MDM2 protein binds both DNA as well as the previously defined RNA consensus sequence., MDM2 SNP309 was not associated with p53 mutational status, MDM2 expression, clinicopathological parameters or prognosis., Atypical lipomatous tumors (ALTs) display supernumerary ring or giant marker chromosomes with amplification of several genes including HMGA2 and MDM2, These findings indicate that the control of HIPK1 stability by Mdm2-NORE1 has a major effect on cell behaviour, and epigenetic inactivation of NORE1 enables adenocarcinoma formation in vivo through HIPK1 stabilization., that MDM2 and MDM4 polymorphisms may influence development and/or survival in RB., Findings suggest that the combination of TP53 72Pro and MDM2 309G polymorphisms enhance the risk of developing HCC., Mdm2 309GG genotype had a higher apoptotic activity compared to TT genotype., Mdm2 inhibited p53-mediated enrichment of HNF4alpha to the ApoCIII promoter while simultaneously reducing p53 binding and increasing recruitment of SHP to the ApoCIII promoter., MDM2 plays an important role in metastasis as well as tumor growth of pancreatic carcinoma., Results suggest that the functional MDM2 T309G genetic variant may play a more important role in carcinogenesis of sarcoma., Suggest a novel apoptotic mechanism of genetically engineered adenovirus-mediated tumour-specific p53 overexpression through E1A-dependent p21 and MDM2 suppression., BCL11B directly interacts with P2 promoter region of HDM2 and inhibits HDM2 promoter activity in a p53-dependent manner., The ATM kinase switches Mdm2 from a negative to a positive regulator of p53 via the p53 mRNA., Results suggest that the MDM2 polymorphism is significantly associated with colorectal cancer risk and may provide useful prognostic information., These findings indicated that the MDM2 indel polymorphism may be a genetic modifier for developing HCC in Chinese population., Downregulation of MDMX results in lower levels of mature and nascent MDM2 transcripts following cellular stress., Significant associations between the MDM2 SNP309T>G and HNSCC risk for TG vs. TT model and the dominant model (TG+GG vs. TT) were observed (OR=0.82, 95%CI=0.70-0.96 and OR=0.83, 95%CI=0.71-0.96, respectively)., Immunohistochemical trio of CDK4, MDM2, and p16 is a useful ancillary diagnostic tool that provides strong support in distinguishing well-differentiated/dedifferentiated liposarcomas from other adipocytic neoplasms., MDM2 and CDK4 coexpression in high-grade osteosarcomas is sensitive and specific to those that progressed from low-grade osteosarcomas, and immunohistochemistry may help identify this dedifferentiated subgroup to facilitate accurate subclassification., Mdm2 may be associated with the invasiveness of laryngeal carcinomas and may represent methodological strategy for the differentiation of in situ carcinoma from laryngeal cancer with metastasis., NS undergoes a ubiquitin- and MDM2-independent proteasomal degradation when intracellular GTP levels are markedly reduced, findings suggest that MDM2 dysregulation caused by downregulation of miR-143 and miR-145 contributes to epithelial cancer development and has a key role in regulating cellular proliferation and apoptosis, The length of the C-terminal regions of Mdm2 proteins has been conserved in evolution, because it can influence their activity toward tumor suppressor p53., No association was observed between MDM2 T309G and esophageal squamous cell carcinoma., in this study we did not find an indication for melanoma recurrence, survival, or an earlier age of onset of melanoma in carriers of either MDM2 SNP309 or TP53 codon 72 Arg/Pro variant alleles., analysis of MDM2 protein-mediated ubiquitination of numb protein, studies identify a tripartite Akt-regulated phosphorylation mechanism that functions to hamper normal ERbeta activity and turnover through the concerted actions of CBP and Mdm2 in response to growth factor signaling pathways in breast cancer cells., Combined WIP1 and HDM2 inhibition is more effective than WIP1 inhibition alone in blocking growth of WIP1 high-expressing medulloblastoma cells., RPS14 and RPS19 have distinct roles in regulating the MDM2-p53 feedback loop in response to ribosomal stress, GS28 forms a complex with the p53 E3 ligase MDM2 in H1299 tumor cells., The peptide inhibitors can produce more interaction contacts with MDM2/MDMX than the non-peptide inhibitors., Current progress in the field about the functional and physical interaction between Mdm2 and Mdmx, their individual and collaborative roles in controlling p53., A mutant SKI defective in transformation fails to increase p53 ubiquitination and is unable to increase MDM2 levels and to increase mono-sumoylation of Ubc9, These results suggested that the MDM2 SNP309 might influence the risk of developing hepatatis B-related hepatocellular carcinoma in a northeast Han Chinese population., Ser17 phosphorylation is functionally neutral with respect to p53 binding, suggesting that MDM2 phosphorylation at a single site is unlikely to play a dominant role in stress-induced p53 activation., In a sample of the Polish population, we observed that the MDM2 285C gene variant may be a significant protective factor against breast cancer., Report low incidence of MDM2 gene amplification in cutaneous and subcutaneous pleomorphic liposarcoma., The Mdm2 protein promotes the NEDDylation of p53beta., Neither MDM2 SNP309 nor SNP285 was associated with lung cancer risk or survival., Furthermore, the combination strategy for disruption of the p53-MDM2 interaction with RT demonstrated enhanced anti-tumor effects both in vitro and in vivo., no evidence indicating that SNP344A may affect MDM2 transcription or cancer risk, study suggest that MDM2 T309G polymorphism might be a low-penetrant risk factor for leukemia among Asians but not Caucasians, These compounds effectively inhibit the E3 ligase activity of the Mdm2-MdmX hetero-complex., High MDM2 is associated with medulloblastomas., Sirt3 overexpression upregulated p53 protein level through downregulating Mdm2 and thereby slowing p53 degradation., Immunohistochemical expression of proteins mdm2 in advanced testicular germ cell tumours, there is a dual role for the Mdm2 acidic domain in the regulation of p53 stability, MDM2 polymorphisms are not involved in myelodysplastic syndrome., Data indicate that TP53/MDM2 alterations were common for advanced tumors within the two circuits., The findings indicate that MDM2 amplif-ication is 93.5% sensitive for diagnosing atypical lipomatous tumor., MDM2 splice variants is significantly assiciated with oral squamous cell carcinoma and increased the risk of oral squamous cell carcinoma development, Novel regulation of MDM2 gene expression by the RNA binding protein RNPC1 via mRNA stability., Findings of the present meta-analysis suggest that the murine double minute 2 309 G allele might be associated with a reduced risk of prostate cancer., A meta-analysis found a significant association between MDM2 SNP309 and breast cancer risk, but no significant combined effects of MDM2 SNP309 and TP53 R72P were observed on breast cancer risk., DNMT3A is transcriptionally repressed, in part, by RB/E2F pathway and that the repression could be attenuated by MDM2 overexpression, Overexpression of p53 causes rapid SHP protein degradation, which does not require the presence of Mdm2 and is mediated by the proteosome pathway, The gene-gene interaction between TP53 Arg72Pro and MDM2 T309G may interact in carcinogenesis of colorectal cancer in Chinese populations., analyses revealed that TP53 Ex2+19C>T and MDM2 309T>G polymorphisms are associated with male infertility and detected a nearly statistically additive interaction between TP53 rs2287498 and MDM2 rs937283 for the development of male infertility, data demonstrate that ribosomal protein S25 is a novel regulator of the MDM2-p53 circuit in ribosomal stress; results shed light on biological consequences of RP-MDM2-p53 interplay and also reveal the existence of a novel S25-p53 feedback regulatory loop, Transcription factor NFAT1 activates the mdm2 oncogene independent of p53., Competitive binding between dynamic p53 transactivation subdomains to human MDM2 protein, TRIAD1 as a novel modulator of the p53-MDM2 axis that induces p53 activation by inhibiting its regulation by MDM2., The results of this study showed that strong association between MDM2 gene alternation and high-grade oligodendroglial tumors., MDM2 overexpression in plexiform ameloblastoma, follicular ameloblastoma and acanthomatous ameloblastoma when compared to simple unicystic and desmoplastic ameloblastoma suggest a relatively enhanced proliferative phenotype., disruption of p53-MDM2 interaction by Nutlin-3a might reduce cell proliferation and promote apoptosis in osteosarcoma with MDM2 amplification and wt p53 status, MDM2 T309G polymorphism might be a risk factor for lung cancer among never-smokers, meta-analysis showed that the MDM2 309G variant was significantly associated with a decreased PCa risk, lower malignant degree and slower clinical progression in Caucasians, but there was no obvious association in the Asian population, Significant association exists between the MDM2 polymorphism and p53 mutation in the Tunisian patients with colorectal cancer., quantify the expression of MDM4 and MDM2 mRNA and protein in human fetal retinae, primary retinoblastomas, retinoblastoma cell lines and several independent orthotopic retinoblastoma xenografts, present meta-analysis of available data showed a significant association between the MDM2 SNP309 T/G polymorphism and liver cancer risk, the MDM2 SNP309 G allele contributing to increased risk in both Asians and Caucasians in a graded, dose-dependent fashion, We analyzed the SNP309 genotype in blood samples and tumor tissue from 57 patients with bone or soft tissue tumors showing amplification of MDM2. We did not observe any constitutional enrichment of the G allele., study demonstrated that TRIAD1 is a ubiquitination target for proteasome-dependent degradation by MDM2; results suggest TRIAD1 degradation by MDM2 suppresses TRIAD1-mediated cell growth; data suggested a novel negative regulatory mechanism of TRIAD1 via MDM2 E3 ligase ubiquitination, Study provides a molecular mechanism of how ATM could govern DNA damage-induced destruction of Mdm2 in part by phosphorylating both Mdm2 and CKIdelta to modulate SCFbeta-TRCP-mediated Mdm2 ubiquitination., revealed that Nutlin-3 mediates the in vivo conversion of NPM from an oligomer to a monomer as an MDM2-dependent phenomenon, with Nutlin-3 stimulating MDM2 binding to a peptide motif derived from the oligomerization interface of NPM, Results indicate that the MDM2 SNP309G allele to increase and the SNP285C allele to reduce the risk of BRCA1 related ovarian cancer., Human breast epithelial cells/cancer cells with wild-type p53 were sensitive to growth inhibition by activated Dmp1, MDM2 amplification is uncommon in Gastrointestinal stromal tumor., TP53, MDM2 and USP7 gene polymorphisms indicates a possible role of TP53 and its regulatory pathway as a risk factor for aneuploidy., The current data suggested that p53 Arg72Pro and MDM2 SNP309 polymorphisms may not contribute to glioma susceptibility., Significant associations of rs6599400 and rs1690916 polymorphisms with bone neoplasms development risk were detected in the untranslated regions of the FGFR3 and MDM2 genes., PAK6 phosphorylates Mdm2 on Thr-158 and Ser-186, which is critical for AR ubiquitin-mediated degradation., studies suggest that age-related posttranslational modifications of p53 limit binding to Mdm2, which frees p53 to stimulate caspase-3, activate apoptosis and trigger the pathogenesis that could lead to age-related macular degeneration, SNPs within MDM2 are associated with increased susceptibility to salivary gland carcinoma., This meta-analysis suggests that the GG genotype of MDM2 SNP309 is associated with HNC risk, different expression patterns and clinicopathologic significance of the p14ARF-Mdm2-p53 pathway did exist between the adenocarcinomas of gastric cardia and distal stomach., We found that the MDM2 G allele has a synergistic effect with P21 codon 31arg allele, where risk of acute myeloid leukemia increased to 6.8 instead of 2.9 with P21 31arg allele alone. The MDM2 T wild allele abolished the risk effect of this P21 allele., The analysis revealed no significant association between MDM2-SNP T309G and prostate cancer risk., The inhibition of the interaction between p53 and MDM2 by a novel Aurora-A-mediated p53 phosphorylation was identified, Data show that arginine at codon72 of p53 and GG genotype at 309 in promoter P2 of MDM2 together reveal a direct proportionality with the tumor grade of cervical cancer along with papillomavirus (HPV) infection infection in postmenopausal women., Results suggest that polymorphisms of MDM2 and p14(ARF) contribute to the interindividual difference in susceptibility to differentiated thyroid carcinoma, either alone or more likely jointly., Inhibition of MDM2-mediated Akt phosphorylation with an Aktphosphorylation- specific inhibitor abrogates its ability to improve cell survival., We found that two of the haplotypes significantly influenced MDM2 promoter activity in a haplotype-specific manner., RPS14 stabilized and activated p53 by inhibiting HDM2-mediated p53 polyubiquitination and degradation, Although the interaction between Notch1 and MDM2 results in ubiquitination of Notch1, this does not result in degradation of Notch1, but instead leads to activation of the intracellular domain of Notch1., The expressions of MDM2 and P16 have a negative correlation in laryngeal squamous cell carcinoma., these findings strongly suggest that DnaJC7 participates in p53/MDM2 negative feedback regulatory pathway, and thereby enhancing the stability and activity of p53., the combined p53 Pro/Pro and MDM2 G/G genotype is associated with increased risk of developing HCC, the initial interaction of p53 with MDM2 is long-lived relative to nutlin, but, unlike nutlin, it takes place at the N- and C termini of the MDM2 protein, away from the binding site, suggestive of an allosteric mechanism of action., Patients with low MDM2 and high JWA expression had a better outcome of survival., The results demonstrated overexpression of MDM2 related to regulatory mechanisms of apoptosis in oral lichen planus, siRNA-MDM2 loaded PMPC-b-PDPA nanoparticles could effectively silence MDM2 protein expression in H2009 cells in a dosage-dependent manner, thus induced cell cycle arrest, apoptosis and growth inhibition via upregulation of p21 and activation of caspase-3., MDM2 SNP309 promoter polymorphism and mutations in p53 were not associated with worse prognosis in this cohort of patients with primary stage T1 urinary bladder carcinoma, The results support the hypothesis that the SNP309 polymorphism of the MDM2 gene may be associated with the incidence of endometrial cancer in the female population., the association between MDM2 309 polymorphism and ovarian cancer risk, Glioblastoma cell miR-17 prolonged tumor cell survival, induced angiogenesis and promoted stem-like cell aggregation by repressing expression of MDM2 and PTEN., enhanced HDM2 expression induced by mutant NPM1 may have a role in MEF/ELF4-dependent leukemogenesis, Modulation of p53 C-terminal acetylation by mdm2, p14ARF, and cytoplasmic SirT2., Subgroup analyses of association between TP53 codon 72 and MDM2 SNP309 polymorphisms and gastric cancer survival, MDM2 amplification was found in all 16 cases of dedifferentiated liposarcoma with homolo-gous lipoblastic differentiation., a stress p53-Mdm2-p300-HDAC1 regulatory network that is activated and stabilised by two regulatory proteins, p300 and HDAC1, is reported., binding of Mdm2 to the Slug mRNA appears to provide a novel mechanism through which Mdm2 promotes tumor progression in a manner independent of the presence of p53., Results suggest that the MDM2 SNP309 polymorphism may be a low-penetrant risk factor for the development of gastric cancer., EGCG promotes MDM2 expression in a p53-dependent manner., MDM2 immunohistochemistry or fluorescence in situ hybridization studies can be used to differentiate between plemorphic fibroma and dermal atypical lipomatous tumor., MDM2 SNP309G allele is associated with an increased risk and poor prognosis of gastric carcinoma in Chinese patients., Data indicate that the immunohistochemical analysis of HMGI-C, CDK4, or MDM2 may help to increase diagnostic accuracy., MDM2 overexpression is associated with patients with persistent disease than among those with recurrent disease., Studied how the K24N mutation affects the affinity, structure, and dynamics of p53 transactivation domain (p53TAD) binding to MDM2., We demonstrated in this case-control study that polymorphisms of TP53 and MDM2 modify the effect of the Ras/ER/MDM2 signaling pathway and thus increase the risk of endometrial cancer., Findings indicate p53-independent roles for MDM2 and HUWE1 in apoptosis and suggest the potential for therapy directed against MDM2 to overcome lapatinib resistance., The T309G singel nucleotide polymorphism may be important to Ewing Sarcoma predisposition., Mdm2 auto-ubiquitination enhances its substrate ubiquitin ligase activity, FEZF2 acted as a histone deacetylase-associated repressor downregulating multiple oncogenes including EZH2 and MDM2, through direct binding to their promoters., Inverse association between GG genotype carriage of MDM2 gene is associated with elevated risk of gastric cancer., Association of MDM2 T309G and p53 Arg72Pro polymorphisms and gastroesophageal reflux disease with survival in esophageal adenocarcinoma., polymorphisms of mouse double minute 2 and P53 genes may be genetic modifiers for developing adult adult acute lymphoblastic leukemia, Used hydrogen/deuterium (H/D) exchange to measure Nutlin-3 binding to the N-terminal domain of MDM2 (MDM2(1-126)) in order to begin to develop dynamic assays that evaluate MDM2 allostery., the G allele of p16 540 C>G and GG genotype of MDM2 SNP309 T>G were found significantly lower in patients compared with controls., Data indicate that MDM2-p53 interaction inhibitor MI-888 is capable of achieving rapid, complete, and durable tumor regression in xenograft models., Data indicate that [indoline-3,2'-thiazolidine] derivatives inhibited in vitro of p53-MDM2 interaction and the cell growth of different tumor cells., Higher MDM2 mRNA expression was found in G/G genotype., FISH-mediated detection of MDM2 amplification is the most useful adjunct in the differential diagnosis of liposarcomas and their morphological mimics., The risk of esophageal SCC increased significantly among patients carrying p53 Arg/Arg, or Arg/Pro and HPV16-seropositivity, but not for MDM2 rs937283., MDM2 can act as a direct negative regulator of NFkappaB by binding and inhibiting p65RelA., Late events such as the loss of RB1 and gain of MDM2 appear to be related to the final mechanisms contributing to the metastatic establishment of osteosarcoma., The expressions of p53 and mdm2 is correlated with the severity of leukoplakia cancer., RPL37, RPS15 and RPS20 regulate the Mdm2-p53-MdmX network but employ different mechanisms to do so., The study demonstrates coordinated regulation of Numb, MDM2 and p53 on cell invasion and migration in pancreatic cancer., The MDM2 285G-309G haplotype is associated with an earlier age of tumour onset in patients with Li-Fraumeni syndrome., the suppression of VEGF expression subsequent to inhibition of MDM2 in p53 mutant cells suggests that MDM2 has a regulatory role on VEGF expression through a p53-independent mechanism., Data suggest that RNPC1 is a critical regulator of Mdm2., Studies suggest that MDM2 SNP309 polymorphism was associated with CRC susceptibility, especially among Asians., MDM2 genetic variants are potentially related to osteosarcoma(OS) susceptibility in Chinese Han population, and might be used as molecular markers for assessing OS susceptibility., Data indicate that stapled alpha-helical peptide ATSP-7041 binds both MDM2 and MDMX with nanomolar affinities and activates the p53 pathway in tumors in vitro and in vivo., there are significant associations of MDM2 SNP309 polymorphism and MDM2 rs1690916 polymorphism with malignant bone tumors., Our results show that MDM2 overexpression, unlike p53 overexpression, is not a significant prognostic factor in overall diffuse large B-cell lymphoma rituximab-CHOP protocol patients., These results indicate that N protein-dependent p53 degradation through the ubiquitin proteasome system is one of the anti-apoptotic mechanisms employed by Hantaan virus N protein., RASSF6-induced apoptosis partially depends on p53. RASSF6 binds MDM2 and facilitates its ubiquitination. RASSF6 depletion blocks the increase of p53 in response to UV exposure and up-regulation of p53 target genes., There is a joint effect of MDM2 SNP309G/G genotype and H. pylori infection for the development of gastric carcinoma., role of full-length MDM2 and MDMX proteins and their isoforms in surgical specimens of well-differentiated/de-differentiated liposarcomas, Our data show that alternative splicing of MDM2 and MDM4 is an important feature of high-grade disease for specific types of rhabdomyosarcoma tumors., the Mdm2-HIF1alpha axis is antagonized by serdementan, which decreases levels of glycolytic enzymes, p53 and MDM2 immuno-reactivity was found to be potentially useful in liposarcoma diagnosis, MDM2 rs2279744 polymorphism is significantly associated with increased risk of hepatocellular carcinoma in East Asians., The MDM2 SNP309 polymorphism may be a risk factor for colorectal cancer in Asians., The degradation of TP53 and MDM2 by the proteasome can be selectively dependent on S5a in human cells., The meta-analysis suggests that MDM2 polymorphisms have some effects on the risk of osteosarcoma but have no effect on the survival of patients with osteosarcoma., Downregulation of Mdm2 by miR-661 augments p53 activity and inhibits cell cycle progression in p53-proficient cells., Data indicate a role for MDM2-C that does not require the inhibition of p53 for increasing cancer cell proliferation and survival., The data reveals a novel pathway, defended by the intra-S-phase checkpoint, by which MDM2 induces unscheduled origin firing and accelerates S-phase entry of cells in the absence of p53., The ribosomal protein L6 binds to and suppresses the E3 ubiquitin ligase activity of HDM2, and subsequently attenuates HDM2-mediated p53 polyubiquitination and degradation., MDM2 SNP309 polymorphism is associated with an increased lung adenocarcinoma risk., These data indicate that the G-variant of the Mdm2 SNP309 might influence the development of a more aggressive tumor phenotype in patients with bladder cancer without affecting the overall tumor risk., MDM2 overexpression induced MMP9 expression in a dose-dependent manner and is associated with a poorer prognosis in invasive ductal breast cancer., AURKA promotes tumor growth and cell survival through regulation of HDM2-induced ubiquitination and inhibition of P53., Treatment of ETV6/RUNX1-positive leukemic cell lines with Nutlin-3, a small molecule that inhibits the MDM2/p53 interaction, arrests their cell cycle and induces apoptosis, XPC W690S pathogenic mutant is specifically defective for MDM2 binding and p53 degradation., MDM2 amplification is associated with intraperitoneal dedifferentiated liposarcoma., Overexpression of Gli1, MDM2 and mutant p53 contributes to the development and progression of pancreatic cancer (PC), and plays an important role in predicting PC patients' prognosis., Subcellular localization of Mdm2 expression should be considered in the evaluation of Mdm2 in breast cancer, data suggest evidence for a major role of MDM2 rs2279744 polymorphism in the carcinogenesis of endometrial cancer, especially among Caucasian populations, Human herpesvirus 6B protein U19 contains a p53 BOX I homology motif for HDM2 binding and p53 stabilization., MDM2 is a direct target of miR-221, and a feed-forward loop is described that sustains miR-221 aberrant expression. Also, miR-221 can activate the p53/mdm2 axis by inhibiting MDM2 and, in turn, p53 activation contributes to miR-221 enhanced expression., The Mdm2 SNP309 G allele is implicated as an important laryngeal squamous cell carcinoma and a vocal leukoplakia protective factor in the Chinese Han Population., The present results showed changes in the immunoexpression of hMLH1, MDM2, and p63 in epithelial cells from premalignant and malignant lip disease, supporting the hypothesis that these alterations are related to the process of lower lip carcinogenesis., study indicates that the MDM2 T309G polymorphism may be an ethnicity-dependent risk factor for digestive tract cancers, especially for the upper gastrointestinal tract malignancies, Genetic variations in radiation and chemotherapy drug action pathways and survival in locoregionally advanced nasopharyngeal carcinoma treated with chemoradiotherapy., The G allele of rs2279744 of MDM2 is associated with a higher risk of developing proliferative vitreoretinopathy., These findings highlight MDM2 as a potential therapeutic target to increase TKI-mediated apoptosis and imply that the combination of PI3K/mTOR inhibitor and TKI might form a novel strategy to combat TKI-resistant BCR-ABL1 positive leukemia., MDM2 isoforms have a role in mutant p53 accumulation and gain-of-function in tumorigenesis, we discovered a new MDM2 interacting protein, DNAJB1, and provided evidence to support its p53-dependent tumor suppressor function., the combination of MDM2 SNP 309 and TP53 Arg72Pro genotypes confers higher risk to develop hepatocellular carcinoma., MDM2 T309G polymorphism was associated gastric cancer risk., suggest evidence for a major role of MDM2 SNP309T>G polymorphism in the carcinogenesis of hepatocellular carcinoma, especially among Caucasian populations, Studies indicate taht the levels and function of murine double minute 2 (MDM2) are regulated at the transcriptional, translational and post-translational levels., The presence of SNP309 does not affect MDM2 expression in neuroblastoma., Data show that NEDD4-1 E3 ligase as a novel component of the tumor suppressor protein p53/proto-oncogene proteins c-mdm2 regulatory feedback loop that controls p53 activity during stress responses., This meta-analysis suggests that MDM2 SNP309 polymorphism contributes to endometrial cancer susceptibility., In conclusion, our study indicates that the combination of TP53 Arg/Arg (rs1042522) and MDM2 TT (rs2279744) genotypes may be a risk factor for recurrent pregnancy loss ., Findings suggest that the combined therapy of Pmp53, a plasmid containing both mdm2 small interfering RNA (Si-MDM2) and the wild-type p53 gene, with zinc is an effective therapeutic strategy., c.+309T > G polymorphism related to risk of cutaneous melanoma, Individuals carrying the MDM2 Del1518rs3730485 and MDM2rs2279744 genotypes were at higher risk for chromosomal damage compared with the wild type genotype., p53 is stabilized in the absence of pVHL and becomes hyperstabilized upon DNA damage, which we propose is because of a novel in vivo interaction revealed between human pVHL and a negative regulator of Mdm2, Another important mechanism by which tumors bypass TP53 functions is via increased levels of two TP53 inhibitors, MDM2, and MDM4, Results sugggest applications in dual-targeting anticancer therapy for MDM2 and anti-apoptotic Bcl-2 family proteins., Suggest that undifferentiated pleomorphic sarcomas with MDM2 amplification are dedifferentiated liposarcomas., MDM2 T309G polymorphism might be a risk factor for cervical cancer among Asians, Mdm2, a downstream effector of p53, attenuates the Warburg effect via ubiquitination and degradation of phosphoglycerate mutase., Cyclophilin B is a novel MDM2 interacting partner., this newly identified p53PIAS3 interaction through the 1-52 amino acid region of p53, reduces p53MDM2 complex formation, which not only increases the half-life of p53, but also its transactivation of target genes., results reveal a novel p53- and Mdm2-independent oncogenic function of Mdmx that provides new insight into the many cancers that overexpress Mdmx., Results show an association between MDM2 SNP309 and an increased risk for hereditary melanoma, especially among women., genetic variants in the PTEN, AKT1, MDM2 and p53 tumor suppressor-oncoprotein network may play roles in mediating the susceptibility to NPC in Chinese populations, G-allele of MDM2 rs2279744 (SNP309) is associated with increased lifespan in females., Mdmx may contribute to the regulation of p53 independently of Mdm2 in breast carcinogenesis, findings provide convincing evidence that the MDM2 T309G polymorphism may contribute to individual differences in NSCLC susceptibility and prognosis, MDM2 rs2279744 and TP53 rs1042522 SNPs were associated with EP-induced high-grade neutropenia in extensive-stage SCLC patients., Analysis of the Mdm2 and MdmX RING domains showed that C449 of Mdm2 located at the Mdm2 RING dimer interface is critical for the stability of the RING dimer structure, while R479 has a role in recruiting and activating the ubiquitin E3 conjugating enzyme., USP15 also stabilized MDM2 in cancer cells and regulated p53 function and cancer-cell survival., meta-analysis demonstrated that the MDM2 SNP309 polymorphism may be associated with increased risk of endometrial cancer, A significant association between MDM2 SNP309 and CRC risk., These findings are the first report describing the regulation of alternative splicing of MDM2 mediated by the oncogenic factor FUBP1., The regulation of Mdm2 by the E3 ubiquitin ligase APC/C is shown. It has important therapeutic implications for tumors with Mdm2 overexpression., HDMX and HDM2 act as nonredundant IRES trans-acting factors to bring a positive synergistic effect on p53 expression., MDM2 serves as a better target for HAUSP-mediated deubiquitination in cancer cells, facilitating degradation of Rb and oncogenic progression., In response to severe DNA damage, p53 phosphorylation at Ser46 is promoted by the accumulation of HIPK2 due to downregulation of nuclear Mdm2 in the later phase of the response., MDM2 phosphorylation and association with protein regulators., MDM2 T309G polymorphism may be significantly associated with increased esophageal cancer risk, especially among Asians., these data show a synergistic effect of MDM2 and E2F1 on TAp73 transcriptional activity, suggesting a novel regulation pathway of TAp73., The orally bioavailable MDM2 antagonist RG7112 and pegylated interferon alpha 2a target JAK2V617F-positive progenitor and stem cells., MDM2 SNP309 mediates affinity of E2F1 which regulates MDM2 expression, CCND1 expression, and cell proliferation in skin cancer., Author show that a negative correlation between miR-339-5p and MDM2 expression exists in human cancer, implying that the interaction is important for cancer development., Polymorphism in MDM2 SNP309 could be correlated to some clinical characteristics and for patients not treated with immunotherapy, a G allele was correlated to poor survival, whereas no survival differences were found for patients treated with Rituximab., large chromosome 12 rearrangement, spanning MDM2 and RASAL1, is the first recurrent molecular abnormality to be reported in juvenile ossifying fibroma, Expression of Mdm2 is a strong prognostic factor associated with shortened overall survival in MPM., depletion of DDX24 in cells impaired pre-rRNA processing and resulted both in abrogation of MDM2 function and in consequent p53 stabilization, determined the effect of ultraviolet B light (UVB) on alternative splicing of hdm2, At the level of protein stabilization via cytoplasmic sequestration of MDM2., netrin-1 promoted pancreatic cancer cell proliferation by upregulation of murine double minute 2 (Mdm2)., Identify a compound called SP141 that reduces levels of MDM2 in pancreatic cancer cell lines, as well as their proliferation and ability to form tumors in nude mice., The genotype for the MDM2 SNP309T>G polymorphism may be associated with genetic susceptibility to bladder cancer., Inhibition of p53 suppression by MDM2 in renal cell carcinoma cells promotes growth arrest and p53-dependent senescence., MDM2 T309G polymorphism may be significantly associated with increased susceptibility to oesophageal or gastric cancer., MDM2-mediated degradation of SIRT6 phosphorylated by AKT1 has a role in promoting tumorigenesis and trastuzumab resistance in breast cancer, The p53-MDM2-MEF axis is a feedback mechanism that exquisitely controls the balance of these transcriptional regulators., This meta-analysis found that MDM2 promoter polymorphism had no influence on disease characteristics and prognosis in chronic lymphocyte leukemia patients., This study shows that the stress-inducible alternative splice forms MDM2-ALT1 and MDMX-ALT2 are important modifiers of the p53 pathway and present a potential mechanism to tailor the p53-mediated cellular stress response., Mathematical simulation of p53-Mdm2 protein biological system regulation is given in various stress conditions, such as in cancer., Our data support the hypothesis of prognostic significance of P53, and double P53/MDM2 positivity in renal cell carcinoma, yet further studies are needed to clarify the issue., MDM2 T309G polymorphism is associated with the risk of liver cancer., We reveal a new mechanism that FOXO3a transcriptionally represses DNMT3B expression and this regulation can be attenuated by MDM2 overexpression in human lung cancer model., miR-410 acted as a new tumor suppressor by targeting the MDM2 gene and inhibiting gastric cancer cells proliferation, migration and invasion., TP53mut analysis and MDM2(SNP309) genotyping may be useful tools for prognostication, risk stratification, and selection of patients most likely to benefit from new drugs targeting the p53 signaling pathway., L-GILZ stabilizes p53 proteins by decreasing p53 ubiquitination and increasing MDM2 ubiquitination., the results of the meta-analysis suggest that the MDM2 T309G polymorphism can increase the risk of leukemia, especially among Asian populations., Because MDM2 amplification and the fusion transcripts PTGES3-PTPRB, HMGA2-DYRK2 and TMBIM4-MSRB3 were found both in the primary tumor and in the metastasis, they are components of the same clone, The data obtained suggest that HIV-infected women are more susceptible to be infected by low-risk HPV (LR-HPV) genotypes than by high-risk (HR-HPV), and Pro72Pro of TP53 gene and TG of MDM2 SNP309 genotypes apparently seem to be protective factors, Relief from Mdm2 suppression is required for p53 to be stabilized and activated in response to stress, Mdm2, p53 and HIF1alpha all respond to hypoxia, and intriguingly, have distinct roles depending on the level of hypoxia, Similar to oncoproteins that induce a DNA damage response and oncogene induced senescence in non-transformed cells, MDM2 induces G1-arrest and intra-S phase checkpoint responses that control untimely DNA replication, Dysregulation of p53-independent functions could be responsible for oncogenic properties of Mdm2 seen even in the absence of p53, and may explain why approximately 10 % of human tumors overexpress Mdm2 instead of inactivating p53 through other mechanisms, review provides a focusing lens for individuals interested in learning about the complexities of mdm2 mRNAs and their protein isoforms as well as the roles MDM2 isoforms may play in cancer progression, focuses on lung cancer stem cells, p53 mutations noted in these cells, and importance of MDM2 interactions, In human primary schwannoma cells p53 was found to be downregulated while MDM2 was upregulated leading to increased cell proliferation and survival, The interaction between the TP63 TT and MDM2 TT genotypes was shown to increase the risk of recurrent pregnancy loss., The G allele of MDM2 was found to be over-represented in patients with gastric cancer compared to controls in this Iranian cohort., MDM2 and SUMO-1 proteins are up-regulated in actinic cheilitis and lip cancer., MDM2 SNP309 has potential as a biomarker of cervical neoplasia in non-smokers, patients with family history of cancer, or those who had late sexual debut, structural information obtained in the present study provides a road map for the rational design of strong inhibitors of MDM2, MDM2 expression was detected in gastric cancer cells which could be inhibited by triptolide., Ribosomal proteins L11 and L5 activate TAp73 by overcoming MDM2 inhibition., Overexpression of MDM2 inhibited Dicer by repressing p63 to create a positive-feedback loop., Evaluation of MDM2 overexpression can be used as a useful adjunct to differentiate well-differentiated liposarcoma from large lipoma and seems to be related with Ki67 proliferation index., Co-occurrence of MDM2 and TP53 SNPs influence risk of endometrial cancer in postmenopausal women., LIF has a role in negatively regulating tumour-suppressor p53 through Stat3/ID1/MDM2 in colorectal cancers, 309 T > G polymorphism might have no significant contribution to susceptibility toward OSCC, A 40-bp ins/del polymorphism in the promoter of MDM2 increased the risk of breast cancer in an Iranian population. The del allele increased the risk of breast cancer (OR = 1.48, 95% CI = 1.11-1.98, P = 0.008) compared with ins allele., Ethnic variation regarding distribution of SNP285C needs to be taken into account when assessing the impact of MDM2 SNPs on cancer risk., This study did not detect any significant differences regarding MDM2 or p53 polymorphisms in Acute Myeloid Leukemia., Increasing residual p53 helicity results in stronger Mdm2 binding, altered p53 dynamics, impaired target gene expression and failure to induce cell cycle arrest upon DNA damage., MDM2 SNP rs2279744 may be significantly associated with increased risk of sarcoma in Caucasian individuals., The authors summarized findings indicating that MDM2 and MDM4 constitute a two-gene family (MDM2 gene family) that belongs to the RING superfamily but have evolved separately from other members of the superfamily. [review], the combined computational and experimental screening protocol presented in this study may also prove useful for screening other commercially-available compound databases for identification of novel, small molecule p53-MDM2 inhibitors., Establish UBTD1 as a regulator of cellular senescence that mediates p53 function, and provide insights into the mechanism of Mdm2 inhibition that impacts p53 dynamics during cellular senescence and tumourigenesis., Report MDM2 expression in thyroid neoplasms., phosphorylated during Chlamydia infection, dependent on a functional MDM2-p53 axis, Association between MDM2 single nucleotide polymorphism and risk of hepatocellular carcinoma in the Han Chinese population, Data indicate that the T309G murine double minute 2 (MDM2) gene polymorphism is an independent prognostic factor for patients with renal cell carcinoma (RCC), with the TT genotype being associated with worse prognosis., MDM2 can inhibit p63 binding to p53R175H but enhances the weaker p53R273H/p73 interaction., Findings argue against a major effect of SNP309 status on the risk for cancer of the breast, prostate, lung or colon. In contrast, a possible tissue speci fi c protective effect of SNP285C was found on cancer risk., electrical stimulation -inducible SIVA1 modulates p53 activities in proliferating keratinocytes, and exogenous electrical stimulation affects p53/HDM2/SIVA1 axis leading to increased proliferation during re-epithelialization, We also discuss the potential diagnostic and prognostic applications of p53 and MDM2 in malignant tumors as well as therapeutic avenues that are being developed to target the MDM2-p53 pathway., We found that the polymorphisms of P53 (rs1042522) and MDM2 (rs2279744) are associated with gastric cancer risk, Akt-Mdm2-p53 signaling involved in the molecular response of gastric epithelial cells to H. pylori infection, we found that the p53 p. Pro72Arg, MDM2 c.14 + 309T > G and MDM2 c.-461C > G polymorphisms are associated with toxicity risks following platinum-based chemotherapy treatment in advanced NSCLC patients., Mir-660 inhibits lung tumorigenesis by targeting MDM2-p53 interaction., MDM2 SNP309 GG genotype is associated with decreased risk of colorectal cancer., The Asp17 mutation in MDM2 stimulated its discharge of the UBCH5a-ubiquitin thioester adduct., The MDM2 c.346G>A genetic variant increases osteosarcoma risk in the homozygote comparison (AA vs. GG), recessive model (AA vs. GA/GG, and allele comparison (A vs. G). The allele-A and genotype-AA are an osteosarcoma risk factor., AMG 232 binds the MDM2 protein., SNP309 polymorphism in the MDM2 gene is associated with susceptibility to leukemia [meta-analysis], Selective inhibition of HDAC2 in lung tumor cell causes survivin downregulation through activation of p53, which is mediated by downregulation of Mdm2., Human gp96 promotes p53 degradation via increasing Mdm2 E3 ligase activity in liver cancer., We found that HDMX-S/FL ratio interacted with p53 mutational status to significantly improve prognostic capability in patients with breast cancer, hMDMX regulates its C-terminal RING domain and the hMDM2 activity., Results show that MDM2 mRNA and protein expression level is elevated in Malignant pleural mesothelioma and significantly correlated with overall and progression-free survival., MDM2 polymorphism may be one of the important factors for the increased expression mdm2, which was associated with down-regulation of p53 and ultimately may contribute in the poor clinical outcome of the non-small cell lung cancer patients, when compared with low-grade central and parosteal osteosarcomas, MDM2 and CDK4 markers cannot be used diagnostically to differentiate this subtype of osteosarcoma, Our study uncovers a new potentially important mechanism through which ARF and MDM2 can counterbalance each other during the tumorigenic process., MDM2 SNP 309 polymorphism might be useful for predicting survival outcome in PDAC patients., JapA represents a new class of MDM2 inhibitor that exerts its anticancer activity through directly down-regulating MDM2., Our study provides new insights into the mechanisms of acquired resistance of Bcl-2 and MDM2 inhibitors in acute leukemia models, The MDM2 309G variation, especially homozygous G/G, might be associated with increased risk of leukemia., Data identify MDM2 and ATRX as new regulators controlling geroconversion, the process by which quiescent cells become senescent., analysis of an MDM2 C-terminal deletion mutant reveals that the C-terminal residues of MDM2 are required for both MDM2 and MDMX interaction., Data indicate that both p53-binding protein oncoprotein MDM2 and MDMX protein bind to p53 through a hydrophobic pocket at the N-terminal domain, but the interactions appear to be regulated differently., highly reliable association of combined susceptible genotypes of polymorphic markers Arg72Pro and T309G of TP53 and MDM2 genes with non small cell lung cancer and both its subtypes., The MDM2-309T>G polymorphism might be involved in acute myeloid leukemia development and also serve as a good prognostic indicator., MDM2 antagonist clinical response association with a gene expression signature in acute myeloid leukaemia., the binding interactions between hDM2 and p53 result in both biosensors becoming co-localized within the nucleolus., we describe the methods and techniques used in the discovery of small-molecule inhibitors of the MDM2-p53 interaction., Murine double minute 2 predicts response of advanced esophageal squamous cell carcinoma to definitive chemoradiotherapy, Binding of XIAP IRES to the RING domain inhibited MDM2 homodimerization., Mdm2 overexpression and p73 loss cooperate in genomic instability and tumor development, indicating that the oncogenic function of Mdm2 is a combined effect of inhibiting p53 and p73 functions, Low expression of PTEN in clearcell renal cell carcinoma contributes to chemoresistance through activating the Akt/HDM2 signaling pathway., Nutlin-induced increase in Mdm2 inhibited DNA double-strand break repair and prolonged DNA damage response signaling independent of p53, MDM2 binds to vitamin D receptor and negatively regulates vitamin D receptor., In conclusion, MDM2 SNP309 may not be associated with the susceptibility of cutaneous melanoma., MDM2 (RS769412) G>A Polymorphism in cigarette smokers is associated with Lung Cancer Risk., Mekk1 mediates p53 protein stability in the presence of Mdm2 and reduces p53 ubiquitination, suggesting an interference with Mdm2-mediated degradation of p53 by the ubiquitin-proteasome pathway., MDM2 mediates p73 ubiquitination, Studied the disordered lid region of the N-terminal domain of MDM2 in the presence of different ligands., data thus show that SJSA-1 tumor cells acquire very different levels of resistance in vitro and in vivo to the MDM2 inhibitor SAR405838., Anti-MDM2 autoantibody was detected at high prevalence in SLE patients. The detection of anti-MDM2 in SLE patients should be clinically useful., Np9 contributes to the regulation of the p53-MDM2 pathway specifically in humans, chimpanzees and gorillas., High expression of MDM2 at mRNA levels is an important factor of neuroblastoma prognosis., FBXO31-mediated loss of MDM2 leads to elevated levels of p53, resulting in growth arrest. In cells depleted of FBXO31, MDM2 is not degraded and p53 levels do not increase following genotoxic stress, We found no significant associations for CDKN2 p16 580 C>T and MDM2 SNP309 T>G variants between cases and controls., Findings indicate molecular simulations of c-mdm2 proto-oncogene protein (MDM2) and its complex with tumor suppressor protein p53 (p53) by explicit-solvent simulations., Report diagnostic utility of FISH testing for MDM2 amplification in problematic lipomatous tumors., Overexpression of microRNA125a3p effectively inhibits the cell growth and invasion of lung cancer cells by regulating the mouse double minute 2 homolog/p53 signaling pathway, CETSA was able to validate stapled peptide binding to Mdm2 and Mdm4., the MDM2 285C gene variant and 285CC/309GG + 285GC/309GG genotypes protect against squamous cell carcinoma., highly expressed HBXIP accelerates the MDM2-mediated degradation of p53 in breast cancer through modulating the feedback loop of MDM2/p53, resulting in the fast growth of breast cancer cells., HAUSP-nucleolin interaction is regulated by p53-Mdm2 complex in response to DNA damage., MDM2 polymorphisms are correlated with the onset of laryngeal carcinoma. The relationship is strengthened by alcohol drinking., MDM2 SNP309 polymorphisms and SNP309G-del1518+ haplotype may significantly contribute to genetic susceptibility to ESCC in the Chinese population., These data show that MTBP aggravates the invasion and metastasis of HCC by promoting the MDM2-mediated degradation of E-cadherin., In the case of not transformed cells MDM2 inhibits double strand brakes (DSBs) repair, hence stimulating carcinogenesis. In cancer cells MDM2 stimulates cytostatic-induced DSBs repair, thus leading to chemoresistance.(review), RG7112 significantly synergized with Trabectedin in MDM2-amplified liposarcoma cells., 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., SNP55, a new functional polymorphism of MDM2-P2 promoter, contributes to allele-specific expression of MDM2 in endometrial cancers., Unleashed expression of Mdm2 in cancer patients with diminished expression of Set7/9 is associated with poor survival outcome., MDM2 Polymorphisms are associated with Head and Neck Cancer., Data show that the ubiquitin-conjugating enzyme E2 RAD6A/B-MDM2 ubiquitin ligase machinery regulates anti-silencing function 1A protein (ASF1A) degradation., The cholesterol metabolite 27-hydroxycholesterol may contribute to ER-positive breast cancer progression by disrupting constitutive p53 signaling in an MDM2-dependent manner., MDM2-309 polymorphism variant genotypes decrease the risk of recurrence in vocal leukoplakia., variant alleles in the NEIL2 (rs804270), APE1 (rs2275008), CYP2E1 (rs2031920) and MDM2 (rs2279744) SNPs may independently influence susceptibility to gastric cancer in a Northern Jiangsu Chinese population., HOTAIR binds to the AR protein to block its interaction with the E3 ubiquitin ligase MDM2, thereby preventing AR ubiquitination and protein degradation thus promoting prostate cancer cell growth and invasion., underscore the importance of TP53 R72P and MDM2 SNP309 SNPs in myelodysplastic syndromes, MDM2 may be less effective than inducing p53-independent cell death, Data show that proto-oncogene protein Mdm2 inactivation successfully protects tumor suppressor protein (p53)-proficient cells against the cytotoxic effects of Wee1 protein inhibition., Both cases positive for MDM2 amplification showed MDM2 expression by immunohistochemistry. At last follow-up, both patients had died of disease, MageB2 counteracts E2F inhibition by ribosomal proteins independently of Mdm2 expression, a correlation between the distinct cytotoxicity of chalcones 1 and 2 and their ability to disrupt the p53-MDM2 interaction was established., the MDM2 SNP309 G/G homozygous genotype might be a risk factor for gastric cancer in Thailand, Data show that TTK protein kinase (hMps1) interacts with proto-oncogene protein MDM2 in vivo and in vitro., Data show that c-mdm2 proto-ocogene protein (MDM2) expression levels were correlated with hypoxia-inducible factor 1, alpha subunit (HIF1alpha) levels, necrosis and proliferation index in malignant pleural mesothelioma., Functional validation demonstrated that TBMS1-induced NCI-H460 cell cytotoxicity involved nucleolar stress-induced p53/murine double minute clone 2 (MDM2), mTOR, and NF-kappaB signaling pathways., The study found the frequency of Mdm2 SNP309 G/G in the Thai population to be very low, and suggests that this can explain to some extent the low incidence of severe inflammation and gastric cancer changes in the Thai population., higher expression in patients with active rheumatoid arthritis correlates with disease activity, A novel interaction between TFII-I and Mdm2 with a negative effect on TFII-I transcriptional activity has been documented., MDM2 supports the PRC2 mediated repression of lineage-specific genes in stem cells, independent of p53., This review will focus on the aberrant splicing of tumor suppressor/oncogenes that belong to the DMP1-ARF-MDM2-p53 pathway, G/G genotype was not associated with tumor recurrence after surgical treatment and it did not show any correlation with other prognostic factors., RNF12 is a novel positive regulator of p53 pathway and an external E3 ubiquitin ligase for MDM2 destruction., Meta-analysis results suggest that homozygote GG alleles of MDM2 SNP309 may be a low-penetrant risk factor for head and neck cancer, and G allele may confer nasopharyngeal cancer susceptibility., results herein have revealed a set of residues R65-E69 on MDM2 proximal to the p53 hydrophobic binding pocket that exhibited an energetic profile deviating significantly from similar residues elsewhere in the protein, we demonstrated that rLZ-8 promoted the interaction between MDM2 and Slug, resulting in Slug degradation, Report a new subtype of high-grade mandibular osteosarcoma with RASAL1/MDM2 amplification., We conducted updated meta-analyses to evaluate the role of MDM2 T309G polymorphism in urinary tract cancer susceptibility., The proposed non-linear feedback control and perturbations compensation method for the p53-mdm2 system can result in more efficient chemotherapy schemes where the infusion of medication will be better administered., Overexpression of MDM2 independently predicted a reduced risk of death in non-small cell lung carcinoma patients.,
OFFICIAL_GENE_SYMBOL MDM2,
OMIM_DISEASE Accelerated tumor formation, susceptibility to,
SP_COMMENT disease:Seems to be amplified in certain tumors (including soft tissue sarcomas, osteosarcomas and gliomas). A higher frequency of splice variants lacking p53 binding domain sequences was found in late-stage and high-grade ovarian and bladder carcinomas. Four of the splice variants show loss of p53 binding., domain:Region I is sufficient for binding p53 and inhibiting its G1 arrest and apoptosis functions. It also binds p73 and E2F1. Region II contains most of a central acidic region required for interaction with ribosomal protein L5 and a putative C4-type zinc finger. The RING finger domain which coordinates two molecules of zinc interacts specifically with RNA whether or not zinc is present and mediates the heterooligomerization with MDM4. It is also essential for its ubiquitin ligase E3 activity toward p53 and itself., function:Inhibits TP53/p53- and TP73/p73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Functions as a ubiquitin ligase E3, in the presence of E1 and E2, toward p53 and itself. Permits the nuclear export of p53 and targets it for proteasome-mediated proteolysis., induction:By DNA damage., miscellaneous:MDM2 RING finger mutations that failed to ubiquitinate p53 in vitro did not target p53 for degradation when expressed in cells., online information:Mdm2 entry, PTM:Auto-ubiquitinated; which leads to proteasomal degradation., PTM:Phosphorylated in response to ionizing radiation in an ATM-dependent manner., similarity:Belongs to the MDM2/MDM4 family., similarity:Contains 1 RanBP2-type zinc finger., similarity:Contains 1 RING-type zinc finger., similarity:Contains 1 SWIB domain., subcellular location:Expressed predominantly in the nucleoplasm. Interaction with ARF(P14) results in the localization of both proteins to the nucleolus. The nucleolar localization signals in both ARF(P14) and MDM2 may be necessary to allow efficient nucleolar localization of both proteins., subunit:Binds p53, p73, ARF(P14), ribosomal protein L5 and specifically to RNA. Can interact also with retinoblastoma protein (RB), E1A-associated protein EP300 and the E2F1 transcription factor. Forms a ternary complex with TP53/p53 and WWOX. Interacts with CDKN2AIP, MTBP, TBRG1, USP7, PYHIN1 and UBXN6. Isoform Mdm2-F does not interact with TP53/p53. Interacts with and ubiquitinates HIV-1 Tat., tissue specificity:Ubiquitous. Isoform Mdm2-A, isoform Mdm2-B, isoform Mdm2-C, isoform Mdm2-D, isoform Mdm2-E, isoform Mdm2-F and isoform Mdm2-G are observed in a range of cancers but absent in normal tissues.,