Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
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SMAD family member 2(SMAD2) SMAD family member 2(SMAD2) Related Genes Homo sapiens
CHROMOSOME 18,
CYTOBAND 18q21.1,
ENSEMBL_GENE_ID ENSG00000175387,
GENERIF_SUMMARY Crystal structure of a phosphorylated Smad2. Recognition of phosphoserine by the MH2 domain and insights on Smad function in TGF-beta signaling, repression of transactivating activity by association with a novel splice variant of CCAAT-binding factor C subunit, c-Jun associates with the oncoprotein Ski and suppresses Smad2 transcriptional activity, activation by transforming growth factor beta in absence of receptor endocytosis, HTLV-1 tax represses Smad-mediated TGF-beta signaling., activation of TGF-beta1/Smad2 signaling is associated with airway remodeling in asthma, Nucleocytoplasmic shuttling of Smads 2, 3, and 4 permits sensing of TGF-beta receptor activity., overexpression of adenoviral Smad1 and Smad2 proteins without exogenously added ligands induced inhibin B production, Levels of phosphorylated Smad2/3 are sensors of the interplay between effects of retinoic acid and TGF-beta or vitamin D3 on monocytic and granulocytic differentiation of HL-60 cells., Phenotypic and functional changes associated with TGF-beta1-induced fibroblast terminal differentiation are differentially regulated by Smad2, Smad3, and Smad4., TGF-beta1 inhibited IFN-gamma and TNF-alpha-induced TARC production in HaCaT cells via Smad2/3. Modulation of TGF-beta/Smad signaling pathway may be beneficial for treatment of atopic dermatitis., In SMAD4-negative cell lines, TGF-beta caused Smad2 to move to the nucleus in a Smad4-independent fashion. Nuclear translocation of Smad2 was not sufficient to activate reporters for TGF-beta-induced transcriptional responses., Results suggest that the Smad 2 may be the downstream signal transducers of TGF-beta(1) in human dental pulp cells., A deletion of 'G' in the L3 loop (crucial in Smad-receptor interaction) & an insertion of 'A' in codon 122 (loss of MH2 domain) in cervical tumor cells caused frame shift & pretermination in Smad2, highlighting its important role in these tumors., a signal transduction cascade of the TGF-beta/Smad signaling pathway, which is activated in the GEC, appears to be involved in the development of focal segmental glomerulosclerosis, Smad2, Smad3 and Smad4 contribute to the regulation of TGF-beta responses to varying extents, and exhibit distinct roles in different cell types, Tuberin (TSC2) interact with smad2/smad3 during TGF-beta1 growth regulation., The most transcriptionally active splice variants of Smad2 are made in macrophages (but not SMCs) of fibrofatty lesions and are upregulated after cell differentiation from monocytes. Cyclin inhibitors are induced by Smads. Fibrous plaque SMCs make Smad2., Differential gene expression of Smad2, a tumor suppressor gene, plays a significant role in the proliferation of breast cancer, Regulated cytoplasmic and nuclear retention may play a role in determining the distribution of Smads between the cytoplasm and the nucleus in both uninduced cells and upon TGF-beta induction., Smad2/3 is activated in undifferentiated human embryonic stem cells and required for the expression of genes controlling Nodal signaling, TGF-beta-stimulation of transcription of PAI-1 is inhibited by VEGF, and TGF-beta phosphorylation of Smad2/3, an obligatory step of intracellular TGF-beta signaling, is suppressed by VEGF, NEDD4-2 bound to TGF-beta-specific R-Smads, Smads 2 and 3, in a ligand-dependent manner, and induced degradation of Smad2, but not Smad3, p38 MAP kinase and Rho/ROCK pathways together with Smad2 and Smad3 are necessary for TGF-beta-mediated growth inhibition, caspase-3 is crucial for the differentiation of bone marrow stromal stem cells by influencing TGF-beta/Smad2 pathway and cell cycle progression, internalization is important for transforming growth factor beta1-induced Smad2 association with Smad anchor for receptor activation (SARA) and Smad2-dependent signaling in human mesangial cells, c-Jun NH(2)-terminal kinase tended to induce the phosphorylation of Smad2/3L in human colorectal adenoma-carcinoma sequence., TGF-beta signaling suppresses nuclear export of Smad4 by chromosome region maintenance 1 and targets Smad4 into the nucleus; mutations in Smad4 that affect its interaction with Smad2 or Smad3 impair nuclear accumulation of Smad4 in response to TGF-beta, UV-induced down-regulation of TbetaRII and the concerted over-expression of Smad7 may trigger the inhibition of the TGF-beta-induced phosphorylation of Smad2., Smad4, but not Smad2, mediates TGF-beta1-induced MMP-2 expression in invasive extravillous trophoblasts, Distinct roles for Smad2 and Smad3 in TGFbeta1-induced CTGF expression and markers of EMT in human PTECs are reported., TGF-beta-dependent nuclear accumulation of Smad2 is caused exclusively by selective nuclear trapping of phosphorylated, complexed Smad2, TGF-beta1 acts on adjacent stromal cells to turn on Smad2 signalling that could lead to stromal decidualization., Babo/dSmad2 signaling prior to metamorphosis may be widely required to prepare neurons for the dynamic environment present during metamorphosis., A novel missense mutation of SMAD2, located in exon 8 at codon 276 TCG (ser) -->TTG (leu), was identified in head and neck squamous cell carcinoma cell line SCC-15., Activation of Smad3 but not Smad2 is a key mechanism by which Angioteinsin ii mediates artriosclerosis., Our data indicate that TGF-beta1 induces endothelial barrier dysfunction involving Smad2-dependent p38 activation, resulting in RhoA activation by possible transcriptional regulation., These results suggest that p38 affects the phosphorylation of Smad2 and Smad3 differentially during TGF-beta signaling in human dental pulp cells and ERK1/2 might be involved in the process., identified the small C-terminal domain phosphatase 1 (SCP1) as a specific phosphatase for Smad2/3 dephosphorylation in the linker and N terminus, mRNA expressed in human granulosa-luteal cells at oocyte retrieval., Leptin and TGF-beta1 synergistically augmented activation of signalling components of mitogen-activated protein kinase (MAPK), STAT3 and Smad but did not modulate the expression of LEPR-B., Disruption of the TGF-beta 1-Smad2 signaling pathway may lead to the resistance of TGF-beta 1 growth-inhibitory effect on oral squamous cell carcinoma., High Smad2 is associated with glioma, Breast cancer wiwthw hight expression of cancerous phosphorylated Smad2 tended to have a better prognosis, although statistic significance was never reached., Platelets possess Smad2 protein and that its phosphorylation state is increased after exposure to TGF-beta1., High D-glucose increases L-arginine transport and eNOS expression following TbetaRII activation by TGF-beta1 involving p42/44(mapk) and Smad2 in HUVEC., Results define Erbin as a novel negative modulator of Smad2/Smad3 functions and expand the physiological role of Erbin to the regulation of TGFbeta signaling., The aberrant expressions of PTEN and phosphorylated Smad2 and their interaction may play an important role in the pathogenesis of hepatocellular carcinoma., Aberrant location of expression/staining intensity of PTEN, PPM1A and P-Smad2 in hepatocellular carcinoma may impact disease progression., Mutant p53 attenuates TGF-beta1 signaling. This was exhibited by a reduction in SMAD2/3 phosphorylation and an inhibition of both the formation of SMAD2/SMAD4 complexes and the translocation of SMAD4 to the cell nucleus., The expression of Smad2/3 in cervical cancer had no correlation to clinical stage, pathologic classification, histological grade, and lymph node involvement, but was positively correlated to HPV16 E7 infection., These findings suggest that CLU regulates TGF-beta signaling pathway by modulating the stability of Smad2/3 proteins., Activin A increased and follistatin decreased phosphorylation of SMAD2/3 in vitro, and activin increased SMAD2 and decreased KITLG mRNA expression., increased TGF-beta-Smad signaling in sporadic and familial ALS and impaired TGF-beta signal transduction in neurons of sporadic ALS patients, presumably at the step of pSmad2/3 translocation into the nucleus, TGF-beta mediates its effects on proteoglycan synthesis in VSMCs via the ALK5/Smad2/3 phosphorylation pathway as well as via the p38 MAP kinase signaling cascade., interaction between RAP250, Smad2, and Smad3 constitutes an important bridging mechanism linking LXR and TGF-beta signaling pathways., SMAD 2/3 signaling directly supports NANOG expression, while SMAD 1/5/8 activation moderately represses SOX2., PTEN abrogates TGF-beta-induced Smad2/3 phosphorylation. This study establishes a novel role for nuclear PTEN in the stabilization of PPM1A., PCTA defines a new component of the TGF-beta signalling pathway that functions to facilitate Smad2 phosphorylation through controlling the accumulation of cPML into the cytoplasm, and consequently, the assembly of Smad2-receptor complex., Data demonstrate that in response to TGFbeta stimulation the transcriptional regulator TAZ binds heteromeric Smad2/3-4 complexes and is recruited to TGFbeta response elements., Compared with normal skin fibroblasts, endogenous expression of Smad2 in hypertrophic skin fibroblasts was up-regulated and TGF-beta1 could further stimulate the production of Smad2., Keratinocyte-specific Smad2 ablation results in increased epithelial-mesenchymal transition during skin cancer formation and progression., the expression levels of TbetaRII and Smad2 in Sertoli Cell-Only Syndrome testes were upregulated compared to that in the normal controls., a number of putative novel Smad2 and Smad3 associated proteins in TGF-beta1 signaling were identified that have functions in cell proliferation, apoptosis, actin cytoskeleton regulation, cell motility, transcription, and Ras or insulin signaling, Activin stimulates endogenous inhibin alpha- and betaB-subunit mRNA, protein, and proteolytic processing. Simultaneously, activin stimulated the proconvertase furin through a Smad2/3-dependent process., SMAD2 is not shown to have a role in colorectal cancer with inflammatory bowel disease, Binding elements for ETS and transcription factor AP-2 (TFAP2) were significantly enriched in Smad2/3 binding sites, and knockdown of either ETS1 or TFAP2A resulted in overall alteration of TGF-beta-induced transcription., This study has demonstrated that constant cyclic stretching inhibits adipogenic differentiation of human umbilical cord progenitor cells via autocrine/paracrine stimulation of the TGFbeta1/Smad2 signaling pathway., Single nucleotide polymorphism in SMAD2 gene is associated with acute lymphoblastic leukemia., Data suggest that integrin alpha3beta1 is a critical coordinator of epithelial-mesenchyme transition signaling pathways involving beta-catenin and pSmad2., Pin1 negatively regulates TGF-beta signaling by down-regulating Smad2/3 protein levels via induction of Smurf2-mediated ubiquitin-proteasomal degradation., disruption of Smad2 function by CDK2 phosphorylation acts as a mechanism for TGF-beta resistance in multiple myeloma., RanBP3 directly recognizes dephosphorylated Smad2/3, which results from the activity of nuclear Smad phosphatases, and mediates nuclear export of Smad2/3 in a Ran-dependent manner., Ang II activation of Smad2 occurs via the AT1 receptor, but not the AT2 receptor, Results show that targeted disruption of the cell surface Cripto/GRP78 complex precludes Cripto activation of MAPK/PI3K and Smad2/3 pathways., The results suggest that 15d-PGJ(2) inhibits TGF-beta-induced CTGF expression by inhibiting the phosphorylation of Smad2., Study shows that Sp1 alone or the combination of Smad2 and Smad4 activated the alpha(1)(I) collagen promoter in transfected LX-2 stellate cells., SARA has a role in regulating cell phenotype and its effects are mediated through modification of the balance between Smad2 and Smad3 signaling, Study data demonstrates downregulated SMAD2 expression in psoriatic skin., Myostatin or 20 ng/mL BMP-11 maintain the colony and cellular morphology of undifferentiated hESC, maintain POU5f1, NANOG, TRA-1-60, and SSEA4 expression, and display increased SMAD2/3 phosphorylation, Data suggest that the SMAD family, possibly through disruption of SMAD1/5 or activation of SMAD2/3 may contribute to the pathogenesis of JGCT in humans., p130Cas is required for mammary tumor growth and transforming growth factor-beta-mediated metastasis through regulation of Smad2/3 activity, TGF-beta-mediated up-regulation of the expression of the integrin subunits alpha(2) and alpha(6) is mainly mediated in MSC by Smad2., Results identify Nedd4L as the ubiquitin ligase in TGF-beta induced phosphorylation of the transcription factors Smad2 and Smad3., Our data provide evidence that TGF-beta signaling patterns vary by age and pathologic features of prognostic significance including ER expression., Data show that upon hypoxia, the TGF-beta-induced phosphorylation of Smad3 was inhibited, although Smad2 remained phosphorylated, and Smad3 was dephosphorylated by PP2A., Smad2 knockdown resulted in a more aggressive breast cancer cells., Of 51 microsatellite stable colon tumors, 7 (14%) lost ACVR2, 2 (4%) ACVR1, and 5 (10%) pSMAD2 expression., Findings reveal a hyperactive TGFbeta-TGFbetaR-Smad2 signaling axis needed to maintain epigenetic silencing of critical EMT genes and breast cancer progression., feasible route for lactoferrin to transduce its antiproliferative effect in HeLa cells, We assessed the immunohistochemical expression profiles of Smad2, P-Smad2, Smad4, and p21/WAF1 proteins in 34 cases of osteosarcoma, BMP6, Smad1, Smad2 mRNA and protein expression were significantly higher in during sickle-cell pathology with orthopedic complications., Smad6 together with Smad2 may be prognostic factors, independent of nodal status in oral SCC after curative resection, Smad2 is rapidly phosphorylated by treatment with lipoic acid within 30 min, enhancing type I collagen synthesis through the activation of Smad signaling., The Smad2/3 pathway is the predominant TGFbeta1 signaling pathway inducing Il6 and inhibiting Il8 release in bronchial epithelial cells., TGFbeta1-induced Smad2 nuclear translocation is negatively regulated by intracellular Ca(2+) in OLI-neu cells and increased intracellular Ca(2+) concentrations block Smad2-mediated transcription of TGFbeta target genes., Smad2 loss causes HGF upregulation via loss of Smad2-mediated transcriptional repression and enhanced Smad3/4-mediated transactivation., Smad2/3 and p38 MAPK differentially regulate TGFB1-induced epithelial-mesenchymal transition in pulmonary epithelial cells., pattern of Smad2 activation supports a model in which TGFbeta/activin signaling is anti-atherogenic in the media of normal artery walls but is equally compatible with an anti-atherogenic or pro-atherogenic response to TGFbeta/activin in neointima of lesions., The Smad2 was highly expressed in VKC conjunctiva in association with TGF-b1., MicroRNA-155 has a role in targeting SMAD2 and modulating the response of macrophages to transforming growth factor-beta, SMAD2 polymorphisms may be one of genetic determinants of BMD in postmenopausal women, These findings indicate that IKKalpha contributes to the tumor-promoting function of the TGFbeta-SMAD signaling pathway in particular cancers., PARP-1 dissociates Smad complexes from DNA by ADP-ribosylating Smad3 and Smad4, which attenuates Smad-specific gene responses and TGF-beta-induced epithelial-mesenchymal transition., A strong negative correlation between LTBP-1 and P-Smad2 immunoreactivity was found, implying that LTBP-1 is not likely to contribute directly to the increased levels of TGF-beta activity in malignant mesothelioma., The expression of p-Smad2 is associated with malignant phenotype and poor prognosis in patients with advanced gastric carcinoma., results indicate that the DeltaNp63 promoter is activated by the keratinocyte-specific TGF-beta signaling mechanism with Smad2 and IKKalpha in squamous cell carcinomas, Data show that the WWP2-N isoform interacts with Smad2 and Smad3, whereas WWP2-C interacts only with Smad7., Activin A-ACVRIB/ALK4-Smad-dependent collagen production was augmented in SSc fibroblasts, suggesting the involvement of this signaling mechanism in systemic sclerosis., Findings offer insights into how MNK1 pathways control translation of cancer-related mRNAs including SMAD2, a key component of the TGF-beta signaling pathway., Smad2 was both preferentially phosphorylated in the linker region and localized to the nucleus in a flow-dependent manner, In malignant cells with a functional TGF-beta signalling pathway Rac1 antagonizes the TGF-beta1 growth inhibitory response and enhances cell migration by antagonistically regulating Smad2 and Smad3 activation, l type-specific target selection by combinatorial binding of Smad2/3 proteins and hepatocyte nuclear factor 4alpha in HepG2 cells., specific inhibition of SMAD-2/3 signaling pathway in hESCs facilitates the conversion of hESCs into multipotent MSCs with fully immunosuppresive and anti-inflammatory properties in vivo, opening up new avenues for potential future clinical applications., In middle cerebral artery occlusion-induced activation of Smad-binding elements (SBEs), a downstream target of Smad 2/3 transcription factors regulates expression of the luciferase reporter., HEB and E2A-bind the SCA motif at regions overlapping SMAD2/3 and FOXH1, we describe TGF-beta signalling through Smad2/3 and the importance of the linker region in the regulation and expression of genes induced by TGF-beta--{REVIEW}, Protein phosphatase PPM1A regulates the nuclear export of Smad2/3 through targeting nuclear exporter RanBP3., Both androgen-sensitive and castration-resistant prostate cancer cell lines demonstrate TGF-beta1-induced phosphorylation and nuclear translocation of Smad2/3 that is robust in metastatic lines., Data suggest that TGF-beta, TGF-betaR1, TGF-betaR2, Smad4, pSmad2/3, and E-cadherin are closely related to tumor-node-metastasis (TNM) stage of colorectal cancer (CRC)., Smad2 copy-number variations are associated with basal cell carcinoma, squamous cell carcinoma in skin cancers., When PI3K/Akt signaling is low, Wnt effectors are activated and function in conjunction with Smad2,3 to promote differentiation, miR-155 may function as a tumor suppressor to regulate gastric cancer cell metastasis by targeting SMAD2, and its downregulation in gastric cancer cells may be partly ascribed to DNA methylation., Data suggest that the formation of transient TIF1gamma-Smad2-Smad4 ternary complexes is the only one that can account for TGF-beta signaling., Data show that dSmad2 directly influences Baboon's phosphorylation of Mad., TGF-beta family signaling through Smads is conceptually a simple and linear signaling pathway, driven by sequential phosphorylation, with type II receptors activating type I receptors, which in turn activate R-Smads [review], The TGF-beta-mediated regulation of CD36, lipoprotein lipase and scavenger receptor-A gene expression was dependent on Smad-2., analysis of the dynamics of TGF-beta and Smad2/Smad3 signaling [review], Immunohistochemical analysis of phosphorylated Smad2 showed nuclear expression in 70% of the osteosarcoma samples at levels comparable to osteoblastoma. Cases with lower expression showed significantly worse disease free survival., Suggest that TGFbeta1/Smad2 signalling pathway of T cells is altered in patients with Behcet's disease., Diseased aortic valve leaflets demonstrated strong immunohistochemical staining for transforming growth factor-beta1 and phosphorylated Smad2/3., The non-canonical increase in Smad linker phosphorylation induced by riluzole could contribute to the modulation of the pro-oncogenic functions of Smad2 and Smad3 in late stage melanomas., The prevalence of SMAD4, SMAD2, and SMAD3 mutations in sporadic CRCs was 8.6% (64 of 744), 3.4% (25 of 744), and 4.3% (32 of 744), respectively., Binding of Activin-A-responsive SMAD2 to the NKX2-1 promoter plays essential role during respiratory endoderm specification., increased activation in thoracic aortic aneurysms, SDC-2 modulates TGFbeta2 transcriptional regulation via Smad2 signaling to facilitate fibrosarcoma cell adhesion., SMAD2 and SMAD3 acetylatation by P300-CBP is mediated by TGFB1 in human lung cancer cells., show that Araf antagonizes mesendoderm induction and patterning activity of Nodal/Smad2 signals in vertebrate embryos by directly inhibiting Smad2 signalling, Findings indicate that Smad2 is a unique integrator of transcription and signaling events and is essential for the maintenance of the mouse and human primed pluripotent stem cell state., Context-dependent responses to Smad2/3 imposed by Polycomb action provide a mechanism for selective gene regulation that can reconcile the apparently conflicting roles of this signaling pathway in pluripotency, differentiation, and reprogramming., The signaling activation triggered by overexpression of Smad2 was dependent on TGF-beta type I receptor, increased p15 and p21 expression, responsible for inhibiting cell cycle entry, resulting in antiproliferative effects on gingival epithelial cells., Smad2 is required for transcription of the aromatase gene in the KGN cells., a nuclear envelope-localized mechanism of inactivating TGF-beta signaling in which MAN1 competes with transcription factors for binding to Smad2 and Smad3 and facilitates their dephosphorylation by PPM1A., a detailed computational model for TGF-beta signalling that incorporates elements of previous models together with crosstalking between Smad1/5/8 and Smad2/3 channels through a negative feedback loop dependent on Smad7., Smad2 regulated protease nexin-1 up-regulation differentiates chronic aneurysm development from acute aortic dissection., Data show that miR-148a downregulated vimentin expression and upregulated E-cadherin expression, suggesting that miR-148a inhibited epithelial-mesenchymal transition (EMT), and the SMAD2 gene was identified as the direct and functional target of miR-148a., miR-18b regulated the TGF-beta1-induced differentiation of miR-18b regulated the TGF-beta1-induced differentiation of hair follicle mesenchymal stem cells into smooth muscle cells by targeting SMAD2 gene., One SNP in the SMAD2 gene having association with chronic otitis media with effusion in study population., Smad2 and PIAS1 proteins were significantly upregulated resulting in dramatically increased interactions between Smad2/4 and PIAS1 in the presence of zinc., TRPV1 potentiates TGFbeta-induction of corneal myofibroblast development through an oxidative stress-mediated p38-SMAD2 signaling loop., inhibition of Smad2/3 by siRNA significantly decreased the production of IL-6 and VEGF in mesenchymal stem cells and induced their osteogenic differentiation, Smad2 promotes the tumor progression by upregulating the CDK2, CDK4, and cyclin E., Glucocorticoids recruit Tgfbr3 and Smad1 to shift transforming growth factor-beta signaling from the Tgfbr1/Smad2/3 axis to the Acvrl1/Smad1 axis in lung fibroblasts., Nodal expression was significantly upregulated in glioma cells when TGF-beta was added, whereas the TGF-beta-induced Nodal expression was evidently inhibited by transfection Smad2 or Smad3 siRNAs., Phosphorylated Smad2 is enriched in recurrent compared with matched-primary ovarian tumors., High expression of IGFBP7 in fibroblasts induced by colorectal cancer cells is co-regulated by TGF-beta and Wnt signaling in a Smad2/3-Dvl2/3-dependent manner., Using a human CTL system model based on a CD8(+)/CD103(-) T cell clone specific of a lung tumor-associated Ag, we demonstrated that the transcription factors Smad2/3 and NFAT-1 are two critical regulators of this process., Galectin-1 stimulates motility of human umbilical cord blood-derived mesenchymal stem cells by downregulation of smad2/3-dependent COL3A1/COL5A1 and upregulation of NF-kappaB-dependent fibronectin/laminin 5 expression., Respiratory exposure to multi-walled carbon nanotubes induced length dependent pulmonary fibrosis and epithelial-derived fibroblasts via TGF-beta1/Smad2 pathway., data suggest that PGE2 had no effects on Smad2 phosphorylation, suggesting that PGE2-mediated Smad2-Smad4 complex formation is independent of TGF-beta signaling, Data indicate that miR-18a could regulate trophoblast Cell invasion via targeting Smad2., Nodal promotes the self-renewal of human colon cancer stem cells and mediate carcinogenesis of human colorectal cancer via an autocrine manner through Smad2/3 pathway., Mutations in SMAD2 may be a cause of as much as 10% of all congenital heart disease., These results suggest that ZNF580 mediates eNOS expression and endothelial cell migration/proliferation via the TGF-b1/ALK5/Smad2 pathway, and thus plays a crucial role in vascular endothelial cells., Data suggest that extracellular signal-regulated kinases ERK1/2 signaling can cross-interact with the transforming growth factor beta2/Smad2/3 and the Jagged-1/Notch-3 signaling in retinal pigment epithelium cells epithelial-mesenchymal transition., The current findings indicate miR-146a plays an important role in skeletogenesis through attenuation of SMAD2 and SMAD3 function., Smad2 and Smad3 are both necessary for the formation of posterior capsular opacification of human lens epithelial cells., In conclusion, this study identifies opposing roles for Smad2 and Smad3 in peritoneal dialysis-associated peritoneal fibrosis, Activin A, B, and AB produce comparable increases in human trophoblast cell invasion by up-regulating N-cadherin expression in a SMAD2/3-SMAD4-dependent manner., Study has revealed miR-27a as a tumor suppressor and has identified SGPP1 and Smad2 as novel targets of miR-27a, linking to STAT3 for regulating cancer cell proliferation, apoptosis and migration in colorectal cancer., miR-136 may play a tumor-suppressive role by repressing EMT and prometastatic traits via targeting Smad2 and Smad3., The expression levels of collagens type I/III, TGF-beta1, Smad2/3/4/7 and PAI-1 (plasminogen activator inhibitor type 1) in gluteal muscle contraction (GMC) patients were measured., A role for decorin and p-Smad-2 in the pathophysiology of fetal membranes and adverse pregnancy outcomes., Lefty reduced the levels of phosphorylated Smad2, Smad3, and ERK1/2, inhibited the proliferation and invasion of glioma cells, and increased their apoptosis., We found that induction of SMAD2 in HCC cells completely abolished the inhibitory effect of NH4Cl on rapamycin-induced autophagy in HCC cells, suggesting that NH4Cl inhibits autophagy of HCC cells through inhibiting SMAD2 signaling., knockdown of Smad3 significantly reduced TGF-beta1-induced Col.I production. These findings were further evident by the results that overexpression of Smad2 attenuated the expression of Col.I and TIMP-1, High p-Smad2 expression in stromal fibroblasts is associated with non-small cell lung cancer., Ca2+- and KCa3.1-dependent processes facilitate "constitutive" alpha smooth muscle actin expression and Smad2/3 signalling in IPF-derived fibroblasts, and thus promote fibroblast to myofibroblast differentiation., Together, our findings defined an essential role for the KMT1E/SMAD2/3 repressor complex in TGFbeta-mediated lung cancer metastasis., A cytoplasmic predominant TGF-betaRII expression pattern and a higher pSmad2 expression were associated with decreased breast cancer survival., Nodal induces signal transduction through the Smad2/3-dependent pathway in vitro. Results that Nodal promotes pancreatic cancer cell migration and invasion and induces epithelial-mesenchymal transition., MicroRNA-10a silencing reverses cisplatin resistance in the A549/cisplatin human lung cancer cell line via the transforming growth factor-beta/Smad2/STAT3/STAT5 pathway, TGF-beta/Smad2/Smad3 signal pathway is involved in glioma tumor cells proliferation and apoptosis., DEANR1 facilitates FOXA2 activation by facilitating SMAD2/3 recruitment to the FOXA2 promoter, smad2 and Erk/Akt have roles in TGF-beta1-induced apoptosis in human gingival epithelial cells, the findings of the present study suggest that H2O2 contributes to HUVEC apoptosis by inducing Nox4-dependent ROS aggregation and activating the TGF-beta1/Smad2 signaling pathway., Induction of neural crest genes by beta-catenin is repressed by SMAD2/SMAD3, ensuring proper lineage specification., These findings uncover a plausible mechanism for NF-kappaB-sustained TGF-beta/Smad activation via miR-148a in glioblastoma., Report inhibition of colorectal cancer stem cell survival and invasive potential by hsa-miR-140-5p mediated suppression of Smad2 and autophagy., study indicated that miR-212/132 functions as tumor suppressor by targeting SMAD2 in cervical cancer, Neovibsanin B utilizes the canonical Smad signalling pathway to stimulate ECM synthesis in human optic nerve head cells., Studies demonstrated that MUC1-mediated JNK activation not only enhances the phosphorylation of Smad2 C-terminal at Ser-465/467 site (Smad2C) through TGF-beta/TbetaRI, but also enhances the phosphorylation of Smad2 linker region at Ser-245/250/255 site., we show, for the first time, that SMAD2 signaling is directly regulated by HDAC6, SMAD2 mutations are associated with arterial aneurysms and dissections, Astragaloside can delay the renal fibrosis process in diabetic mice by influencing the TGF-beta/SMADS signaling pathway and down-regulating TGF-beta1, SMAD2/3, and alpha-SMA expression., Suggest that TGF-beta1/Smad and Wnt/CTNNB1 signaling pathways both contribute to pathological scar formation., Different signaling pathways are involved in osteitis in CRS and are activated by the TGF-beta/Smad signaling pathway in CRSwNP versus the TGF-beta/Smad-independent signaling pathway in CRSsNP., Follistatin-like 1 attenuates differentiation and survival of erythroid cells through Smad2/3 signaling., Relationship between Expression of TGF-beta1, Smad2, Smad4 and Prognosis of Patients with Resected Non-small Cell Lung Cancer, Up-regulation of smad2 is associated with endometrial cancer., TGF-beta/Smad signalling pathway and VEGF-A participate in the pathogenesis of sarcoidosis., The present study thus proposed SEB as an agent able to significantly reduce Smad2/3 expression in colon cancer cells, provoking moderate TGFb growth signaling and the reduction of tumor cell proliferation., Data suggest SHC1 (SH2 domain protein C1) expression down-regulates epithelial-mesenchymal transition by repressing TGFB-induced SMAD2/3 activation through differential partitioning of receptors at cell surface of mammocytes/keratinocytes., correlation between TGFb1 and pSmad2 as well as between HtrA1 and TGFb1 and the very significant increase of Ki67 in stromal compartment of eutopic endometrium suggest a possible involvement of HtrA1 in the pathogenesis of endometriosis., data suggest that TGF-beta1 enhances IGFBP7 via Smad2/4 pathways, and that IGFBP7 might be involved in the TGF-beta1-induced tubular injury in DN.,
SP_COMMENT disease:Defects in SMAD2 are found in sporadic cases of colorectal carcinoma., function:Transcriptional modulator activated by TGF-beta and activin type 1 receptor kinase. SMAD2 is a receptor-regulated SMAD (R-SMAD). May act as a tumor suppressor in colorectal carcinoma., PTM:Acetylated on Lys-19 by coactivators in response to TGF-beta signaling, which increases transcriptional activity. Isoform short: Acetylation increases DNA binding activity in vitro and enhances its association with target promoters in vivo., PTM:In response to TGF-beta, ubiquitinated by NEDD4L; which promotes its degradation., PTM:Phosphorylated on one or several of Thr-220, Ser-245, Ser-250, and Ser-255. In response to TGF-beta, phosphorylated on Ser-465/467 by TGF-beta and activin type 1 receptor kinases. Able to interact with SMURF2 when phosphorylated on Ser-465/467, recruiting other proteins, such as SNON, for degradation. In response to decorin, the naturally occurring inhibitor of TGF-beta signaling, phosphorylated on Ser-240 by CaMK2. Phosphorylated by MAPK3 upon EGF stimulation; which increases transcriptional activity and stability, and is blocked by calmodulin., similarity:Belongs to the dwarfin/SMAD family., similarity:Contains 1 MH1 (MAD homology 1) domain., similarity:Contains 1 MH2 (MAD homology 2) domain., subcellular location:Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with SMAD4., subunit:Found in a complex with SMAD3 and TRIM33 upon addition of TGF-beta. Interacts with SMAD3 and TRIM33. Interacts with SARA (SMAD anchor for receptor activation); may form trimers with the SMAD4 co-SMAD. Interacts with FOXH1, homeobox protein TGIF, PEBP2-alpha subunit, CREB-binding protein (CBP), EP300 and SKI. Interacts with SNON; when phosphorylated at Ser-465/467. Interacts (via PY-motif) with SMURF2. Interacts with AIP1 and HGS. Interacts with NEDD4L in response to TGF-beta (By similarity). Interacts with LBXCOR1 and CORL2., tissue specificity:Expressed at high levels in skeletal muscle, heart and placenta.,
SMAD family member 3(SMAD3) SMAD family member 3(SMAD3) Related Genes Homo sapiens
CHROMOSOME 15,
CYTOBAND 15q22.33,
ENSEMBL_GENE_ID ENSG00000166949,
GENERIF_SUMMARY repression of transactivating activity by association with a novel splice variant of CCAAT-binding factor C subunit, HTLV-1 tax represses Smad-mediated TGF-beta signaling., Smad3 trimerization, induced by phosphorylation, activates the TGF-beta signal by driving Smad3 dissociation from SARA & sets up the negative feedback mechanism by Ski., Data suggest that SMAD3 interactions with the positive regulators NKX2.1 and HNF-3 underlie the molecular basis for TGF-beta-induced repression of surfactant protein B gene transcription., Smad3 is unlikely to function as a classical tumor suppressor gene in the pathogenesis of sporadic parathyroid or enteropancreatic endocrine tumors., Nucleocytoplasmic shuttling of Smads 2, 3, and 4 permits sensing of TGF-beta receptor activity., interactions between AR, Smad3, and Smad4 may result in the differential regulation of the AR transactivation, which further strengthens their roles in the prostate cancer progression, adenovirally-expressed Smad3 augmented the TGF-beta-elicited induction of MMP-13 expression, Levels of phosphorylated Smad2/3 are sensors of the interplay between effects of retinoic acid and TGF-beta or vitamin D3 on monocytic and granulocytic differentiation of HL-60 cells., HTLV1 Tax inhibits TGF-beta1 signaling by reducing the Smad3 DNA binding activity, autocrine regulation of TGF-beta2 production in endothelial cell hypoxia may involve cross-talk between Smad3 and hypoxia inducible factor-1alpha signaling pathways, Phenotypic and functional changes associated with TGF-beta1-induced fibroblast terminal differentiation are differentially regulated by Smad2, Smad3, and Smad4., TGF-beta1 inhibited IFN-gamma and TNF-alpha-induced TARC production in HaCaT cells via Smad2/3. Modulation of TGF-beta/Smad signaling pathway may be beneficial for treatment of atopic dermatitis., In SMAD4-negative cell lines, TGF-beta caused Smad3 to move to the nucleus in a Smad4-independent fashion. Nuclear translocation of Smad3 was not sufficient to activate reporters for TGF-beta-induced transcriptional responses., Results suggest that the transcriptional cross talk between the TGFbeta-regulated Smads 3 and 4 and hepatocyte nuclear factor-4 is mediated by specific functional domains in the two types of transcription factors., stimulates basal and Tat-mediated transcription of MCP-1 in human astrocytic cells, Mediation of tumor growth factor beta-1 induced collagen I expression in glomerular mesangial cells., Down-regulation of Smad 3 expression by TGF-beta(1) at later stage is involved in negative modulation of TGF-beta(1) signaling., SMAD3 has a role in regulating TGF-beta expression along with PIASy, Protein and mRNA levels of SMAD3, but not of SMAD4 or SMAD7, were variably elevated in scleroderma fibroblasts, A surface hydrophobic corridor within the MH2 domain of Smad3 is critical for association with CAN/Nup214 and nuclear import; Smad3 and Smad4 have different susceptibility to inhibition of import by cytoplasmic retention factor SARA, smad3 interacts directly with YB1 during TGFbeta signal inhibition by interferon gamma, Smad3 gene mutations could be associated with the pathogenesis of human osteoarthritis, a signal transduction cascade of the TGF-beta/Smad signaling pathway, which is activated in the GEC, appears to be involved in the development of focal segmental glomerulosclerosis, Smad2, Smad3 and Smad4 contribute to the regulation of TGF-beta responses to varying extents, and exhibit distinct roles in different cell types, SMAD3 and SMAD4 activate gadd45beta through its third intron to facilitate G2 progression following TGFbeta treatment, TGF-beta and Smad3 mediate beta-hydroxybutyrate(HB)-induced cell cycle-dependent growth inhibition while Smad3 mediates beta-HB-induced collagen production and p21WAF1/p27kip1 protein expression in human proximal tubule (HK-2) cells., Smad3 expression may have a critical role in tumor suppression in the early stages of gastric carcinogenesis., PIAS3 and Smad3 interact with each other at the endogenous protein level in mammalian cells and also in vitro, and the association occurs through the C-terminal domain of Smad3., a novel, functional binding element in the proximal region of the TN-C promoter mediating responsiveness to TGF-beta involving Smad3/4, Sp1, Ets1, and CBP/p300, Analysis of the human SMAD3 promoter demonstrates that isoprenoid regulation of SMAD3 expression is dependent on Sp1/Sp3 activity, Tuberin (TSC2) interact with smad2/smad3 during TGF-beta1 growth regulation., Smad3 has a role in Activin receptor-like kinase-7 induces apoptosis through activation of MAPKs, menin and TGF-beta/Smad3 negatively regulate the BMP-2/Smad1/5- and Runx2-induced transcriptional activities leading to inhibition of cell differentiation, The most transcriptionally active splice variants of Smad3 are made in macrophages (but not SMCs) of fibrofatty lesions and are upregulated after cell differentiation from monocytes. Cyclin inhibitors are induced by Smads. Fibrous plaque SMCs make Smad3., Gly-BSA increases DNA binding activity of Smad3 and that it stimulates PAI-1 transcription through Smad-binding CAGA sequences in the PAI-1 promoter in human mesangial cells, Our findings suggest that BAMBI transcription is regulated by TGF-beta signaling through direct binding of SMAD3 and SMAD4 to the BAMBI promoter., sphingosine 1-phosphate receptors and the transforming growth factor beta-type I receptor serine/threonine kinase are essential for activation of Smad3 by lysophospholipids, Smad2/3 is activated in undifferentiated human embryonic stem cells and required for the expression of genes controlling Nodal signaling, HCV viral proteins interact with the TGF-beta signaling mediator Smad3 and differentially impair TGF-beta/Smad3-mediated transactivation and growth inhibition., TGF-beta-stimulation of transcription of PAI-1 is inhibited by VEGF, and TGF-beta phosphorylation of Smad2/3, an obligatory step of intracellular TGF-beta signaling, is suppressed by VEGF, p38 MAP kinase and Rho/ROCK pathways together with Smad2 and Smad3 are necessary for TGF-beta-mediated growth inhibition, Smad3 induces chondrogenesis through the activation of SOX9 via CREB-binding protein/p300 recruitment, Transforming growth factor-beta1 stimulation of vascular endothelial growth factor production by fibroblasts is regulated by Smad3 but not by Smad2 signaling, c-Jun NH(2)-terminal kinase tended to induce the phosphorylation of Smad2/3L in human colorectal adenoma-carcinoma sequence., TGFbeta1/Smad3 suppresses BRCA1-dependent DNA repair in response to a DNA damaging agent, TGF-beta signaling suppresses nuclear export of Smad4 by chromosome region maintenance 1 and targets Smad4 into the nucleus; mutations in Smad4 that affect its interaction with Smad2 or Smad3 impair nuclear accumulation of Smad4 in response to TGF-beta, TGF-beta/Smad3 signaling is required for hypoxia-mediated inhibition of adipocyte differentiation in marrow stromal cells, Tsc-22 binds to and modulate the transcriptional activity of Smad3 and Smad4, lysine residues of Smad3 MH2 domain play important roles in the transcriptional regulation of TGF-beta signals through TbetaR-I, interleukin-1beta and its downstream mediator mitogen-activated protein kinase kinase kinase 7 inhibit SMAD3-mediated TGFbeta target gene activation, TGF-beta1 and bleomycin intracellular signaling through autocrine regulation of Smad 3 binding to the proximal promoter of the Smad 7 gene, deletion constructs of the promoter and mutational deletion of specific transcription factor binding sites indicated that Smad3/4 and AP-1 binding sites mediated the TGF-beta1 response on LTBP-3, Distinct roles for Smad2 and Smad3 in TGFbeta1-induced CTGF expression and markers of EMT in human PTECs are reported., TGF-beta1 acts on adjacent stromal cells to turn on Smad3 signalling that could lead to stromal decidualization., These observations, together with the finding that CILP protein binds and inhibits TGF-beta1, suggest that CILP and TGF-beta1 may form a functional feedback loop that controls chondrocyte metabolism., A short peptide representing the minimal interaction domain in Smad3 effectively competes with Smad3 association to exportin 4 and blocks nuclear export of Smad3 in vivo., summary of the recent understanding of Smad3 phosphoisoform-mediated signaling, particularly 'cross-talk' between Smad3 and JNK pathways that cooperatively promote oncogenic activities in colorectal carcinogenesis [review], role in nuclear translocation of beta-catenin, Activation of Smad3 but not Smad2 is a key mechanism by which Angioteinsin ii mediates artriosclerosis., One mechanism for positive regulation of TLR2 induction involves functional cooperation between the TGF-betaR-Smad3/4 pathway and NF-kappaB pathway. Another involves (MKP-1)-dependent inhibition of p38 MAPK, a known negative regulator for TLR2 induction, TGFbeta suppresses TERT by Smad3 interactions with c-Myc and the hTERT gene, a novel mutation was found to result in the inhibition of translocation of Smad3 protein to the nucleus and a reduction in the activity of Smad3 during TGF-beta-induced transcriptional activation, These results suggest that RACK1 modulates transcription of alpha2(I) collagen by TGF-beta1 through interference with Smad3 binding to the gene promoter., These results suggest that p38 affects the phosphorylation of Smad2 and Smad3 differentially during TGF-beta signaling in human dental pulp cells and ERK1/2 might be involved in the process., identified the small C-terminal domain phosphatase 1 (SCP1) as a specific phosphatase for Smad2/3 dephosphorylation in the linker and N terminus, mRNA expressed in human granulosa-luteal cells at oocyte retrieval., SHP is a novel co-regulator of Smad3 that regulates TGF-beta signaling, Leptin and TGF-beta1 synergistically augmented activation of signalling components of mitogen-activated protein kinase (MAPK), STAT3 and Smad but did not modulate the expression of LEPR-B., These data lead to the conclusion that MEK1 is an important regulator of SMAD3 expression., Smad3 appears to be important in colonic inflammation., These results suggest that TGFbeta Smad3-dependent signalling is perturbed in Barrett's carcinogenesis, resulting in failure of growth-arrest., Neurofibrillary tangles sequester pSmad3, preventing its translocation into the nucleus and the induction of gene transcription. Interference with the Smad signaling may adversely affect survival of tangle-bearing neurons in AD., The TGFB/SMAD3 signaling pathway is involved in butyrate-mediated vitamin D receptor expression., examined the possible deterioration in the pathway in human squamous cancer cell lines, focusing on intracellular localization of S100C/A11 and its functional partners Smad3 and Smad4-, Results show that Arkadia specifically activates transcription via Smad3/Smad4 binding sites by inducing degradation of the transcriptional repressor SnoN., Results define Erbin as a novel negative modulator of Smad2/Smad3 functions and expand the physiological role of Erbin to the regulation of TGFbeta signaling., Inhibition of beta-catenin resulted in increased TGF-beta1-dependent Smad3 phosphorylation and restoration of TGF-beta1 anti-proliferative effects., transforming growth factor-beta has a role in Smad3-dependent activation of Gli2 and Gli1 expression, findings suggest that CEA (CEACAM5) and CEACAM6 are major target genes for Smad3-mediated TGF-beta signaling., ALK5-dependent Smad3 signaling is the responsible pathway inducing CTGF expression., SMAD3 dependent inactivation of CYP17 promoter activity and repression of SF-1 expression., Mutant p53 attenuates TGF-beta1 signaling. This was exhibited by a reduction in SMAD2/3 phosphorylation and an inhibition of both the formation of SMAD2/SMAD4 complexes and the translocation of SMAD4 to the cell nucleus., Smad3, through regulating angiogenic molecule expression in tumor cells, is critical for progression of prostate cancer, TGFbeta1 represses CYP7A1 gene transcription in human hepatocytes by a mechanism involving Smad3-dependent inhibition of HNF4alpha and histone deacetylase remodeling of CYP7A1 chromatin., The expression of Smad2/3 in cervical cancer had no correlation to clinical stage, pathologic classification, histological grade, and lymph node involvement, but was positively correlated to HPV16 E7 infection., Recent studies highlighted in this review suggest that TGF-beta suppresses neoplastic cell development by employing Smad3 protein to repress the human telomerase reverse transcriptase gene., functional characterization of a tumorigenic mutation in Smad4(E330A); findings show this mutant & a Smad3 mutant (Smad3 E239A) failed to activate transcription in response to TGFbeta stimulation because of defects in oligomerization, SARS coronavirus nucleocapsid protein interacts with Smad3 and modulates transforming growth factor-beta signaling, Thus, SMCX is a novel Smad3 corepressor that may antagonize the tumor suppressing activity of the TGF-beta/Smad3 signaling pathway and thereby contribute to tumorigenesis., These findings suggest that CLU regulates TGF-beta signaling pathway by modulating the stability of Smad2/3 proteins., sequencing of exon 2 of the Smad3 gene disclosed single nucleotide polymorphism, Activin A increased and follistatin decreased phosphorylation of SMAD2/3 in vitro, and activin increased SMAD2 and decreased KITLG mRNA expression., TGF-beta(1) regulates proliferation through Smad3 signaling in both fibroblast populations; however, it is the levels of HA generated by the cells that influence the outcome of this response., TGF-beta-mediated activation of the ALK5-Smad 3 pathway plays a role in SHH promoted motility and invasiveness of gastric cancer cells, myostatin enhanced nuclear translocation of beta-catenin and formation of the Smad3-beta-catenin-TCF4 complex, together with the altered expression of a number of Wnt/beta-catenin pathway genes in hMSCs, increased TGF-beta-Smad signaling in sporadic and familial ALS and impaired TGF-beta signal transduction in neurons of sporadic ALS patients, presumably at the step of pSmad2/3 translocation into the nucleus, TGF-beta mediates its effects on proteoglycan synthesis in VSMCs via the ALK5/Smad2/3 phosphorylation pathway as well as via the p38 MAP kinase signaling cascade., tagln is a novel target of TGF-beta/Smad3-dependent gene expression in alveolar epithelial type II cells, AMPK inhibits TGFbeta-induced transcription downstream of Smad3 COOH-terminal phosphorylation and nuclear translocation, interaction between RAP250, Smad2, and Smad3 constitutes an important bridging mechanism linking LXR and TGF-beta signaling pathways., both ALK1 and ALK5 are needed for TGF-beta-induced phosphorylation of intracellular mediators Smad1/5, whereas only ALK5 is essential for TGF-beta1-induced phosphorylation of Smad3, Coexpression of Smad3 with PIASy and SUMO1 stimulated the nuclear export of Smad3., SMAD 2/3 signaling directly supports NANOG expression, while SMAD 1/5/8 activation moderately represses SOX2., A case-control study in Afro-Caribbeans found SMAD3 SNPs were not strongly associated with increased risk of developing keloids., PTEN abrogates TGF-beta-induced Smad2/3 phosphorylation. This study establishes a novel role for nuclear PTEN in the stabilization of PPM1A., the TGF-beta1-2-3/Smad3 pathway has a role in mediating ovarian oncogenesis by enhancing metastatic potential, Data demonstrate that in response to TGFbeta stimulation the transcriptional regulator TAZ binds heteromeric Smad2/3-4 complexes and is recruited to TGFbeta response elements., a number of putative novel Smad2 and Smad3 associated proteins in TGF-beta1 signaling were identified that have functions in cell proliferation, apoptosis, actin cytoskeleton regulation, cell motility, transcription, and Ras or insulin signaling, SMAD3 is one important transcription factor mediating transforming growth factor beta's- inhibitory effects on IFN-gamma production and antibody-dependent cellular cytotoxicity following CD16 activation of natural killer cells., TGF-beta1 and SMAD3 may be involved in the pathology of corneal diseases associated with herpes simplex virus type 1 infection., Galectin-1 decreases Smad3-complex from binding to the SBE, down-regulating transcription of COL1A2 in TGF-beta1-stimulated renal epithelial cells., Ligand-dependent ubiquitination of Smad3 is regulated by CK1g2, an inhibitor of TGF-beta signaling., Activin stimulates endogenous inhibin alpha- and betaB-subunit mRNA, protein, and proteolytic processing. Simultaneously, activin stimulated the proconvertase furin through a Smad2/3-dependent process., Binding elements for ETS and transcription factor AP-2 (TFAP2) were significantly enriched in Smad2/3 binding sites, and knockdown of either ETS1 or TFAP2A resulted in overall alteration of TGF-beta-induced transcription., Arginine 279, glutamic acid 246 in Smad3 and glutamic acid 1321 in Erbin are important for these proteins binding., Smad3 stimulated the Sox9-mediated transcription in a TGF-beta-dependent manner., Single nucleotide polymorphism in SMAD3 gene is associated with acute lymphoblastic leukemia., These data indicate that the intracellular glutathione redox status regulates TGF-beta-induced fibrogenic effects through Smad3 activation., FoxL2 and Smad3 coordinately regulate follistatin gene transcription.(, Pin1 negatively regulates TGF-beta signaling by down-regulating Smad2/3 protein levels via induction of Smurf2-mediated ubiquitin-proteasomal degradation., part of the variance in SMAD3 expression was gender related as women expressed lower levels of SMAD3 transcripts than men., TGF-beta-induced phosphorylation of Smad3 linker sites inhibits its antiproliferative activity, Hepatitis B virus X protein shifts hepatocytic TGF-beta signaling from the tumor-suppressive pSmad3C pathway to the oncogenic pSmad3L pathway in early carcinogenic process., TGF-beta/Smad3 signaling as an important regulator of insulin gene transcription and beta-cell function and suggest that components of the TGF-beta signaling pathway may be dysregulated in diabetes., RanBP3 directly recognizes dephosphorylated Smad2/3, which results from the activity of nuclear Smad phosphatases, and mediates nuclear export of Smad2/3 in a Ran-dependent manner., Sustained co-cultivation with human placenta-derived MSCs enhances SMAD3 signaling in human breast epithelial cells, leading to EMT and differentiation., Characterization of primary and restenotic atherosclerotic plaque from the superficial femoral artery, Results show that targeted disruption of the cell surface Cripto/GRP78 complex precludes Cripto activation of MAPK/PI3K and Smad2/3 pathways., Transforming growth factor-beta induces phosphorylation at three sites in the Smad3 linker region in addition to the two C-terminal residues, and glycogen synthase kinase 3 is responsible for phosphorylation at one of these sites, namely Ser-204., (PPAR)delta regulates extracellular matrix synthesis and degradation through transforming growth factor-beta1 and its effector, Smad3, Data suggest that Smad3 can regulate acetylcholinesterase transcriptional activation following calcium-induced nuclear accumulation., Akt, activated downstream from ERK 1/2, was required for TGF-beta1-induced ZEBRA expression and enabled Smad3, a mediator of TGF-beta1 signaling, to be acetylated by direct interaction with the co-activator CREB-binding protein, Data show that inhibition of TACE activity or expression enhanced the cell surface TbetaRI levels and TGF-beta-induced Smad3 and Akt activation., genetic variation in SMAD3 alters the susceptibility of an individual to atopic dermatitis., SARA has a role in regulating cell phenotype and its effects are mediated through modification of the balance between Smad2 and Smad3 signaling, Smad signaling pathway plays in important role in the progress of glomerular sclerosis, renal tubular injury and interstitial fibrosis in children with IGA nephropathy., Myostatin or 20 ng/mL BMP-11 maintain the colony and cellular morphology of undifferentiated hESC, maintain POU5f1, NANOG, TRA-1-60, and SSEA4 expression, and display increased SMAD2/3 phosphorylation, loss or reduction of BRCA1 alters TGF-beta growth inhibiting activity via Smad3 during oxidative stress responses, Data suggest that the SMAD family, possibly through disruption of SMAD1/5 or activation of SMAD2/3 may contribute to the pathogenesis of JGCT in humans., p130Cas is required for mammary tumor growth and transforming growth factor-beta-mediated metastasis through regulation of Smad2/3 activity, Results identify Nedd4L as the ubiquitin ligase in TGF-beta induced phosphorylation of the transcription factors Smad2 and Smad3., Data show that upon hypoxia, the TGF-beta-induced phosphorylation of Smad3 was inhibited, although Smad2 remained phosphorylated, and Smad3 was dephosphorylated by PP2A., TGF-beta induction of key target genes involved in bone metastasis, were found to be dependent on Smad3 but not Smad2., High levels of Smad3 are required for the tumor suppressor activities of TGF-beta, whereas lower levels are sufficient for the tumor promoting functions., Data show that S100A4 binds to Smad3 in a Ca2+-dependent manner, potentiates transcriptional activity of Smad3 and the related Smad2, and increases TGF-beta-induced MMP-9 expression., BMP-7 prevents TGF-beta-mediated loss of the transcriptional repressor SnoN and hence specifically limits Smad3 DNA binding., Smad3 prevents beta-catenin degradation and facilitates beta-catenin nuclear translocation in chondrocytes, Smad3 is involved in fibrogenic TGF-ss signaling; its expression is reduced in monocytes, programmable cells of monocytic origin, and neohepatocytes from alcoholic liver disease patients and controls., JNK/Smad3 pathway plays a critical role in TGF-beta1-induced FXII expression in human lung fibroblasts, This study is the first to show that TGF-beta induces CTGF expression through activation of Smad3 and activator protein 1 (AP-1) signaling pathways in nucleus pulposus cells., These data show that the rs28683050 polymorphism of the Smad3 gene may be associated with chronic obstructive pulmonary disease., genetic variation in the SMAD3 gene is involved in the risk of both hip and knee osteoarthritis in European populations, Smad3 regulates RhoA activation and cytoskeletal reorganization by controlling NET1 in TGF-beta1-induced ARPE-19 cells., These results uncovered a novel mechanism for the GSK3beta negative regulation of TGF-beta1/Smad3 and Angiotensin II/ Smad3-mediated transcription and apoptosis by the identification of a crosstalk between GSK3beta and Smad3 signal pathway., Oncogenic Smad3 signaling induced by chronic inflammation is an early event in ulcerative colitis-associated carcinogenesis., The Smad2/3 pathway is the predominant TGFbeta1 signaling pathway inducing Il6 and inhibiting Il8 release in bronchial epithelial cells., Smad3 phosphorylation releases cyclin D1-regulated blockade of Smad3 transcriptional activity and recovered cell cycle arrest in breast cancer cells., Data suggest that deregulated/enhanced expression and activation of AR in prostate carcinomas may intercept the tumor suppressor function of TGF-beta through transcriptional suppression of Smad3., Smad2/3 and p38 MAPK differentially regulate TGFB1-induced epithelial-mesenchymal transition in pulmonary epithelial cells., GDF-9 can promote the motile and adhesive capacity of PC-3 prostate cancer cells by up-regulating expression of FAK and paxillin in a Smad dependent manner, suggesting a pro-tumourigenic role for GDF-9 in prostate cancer., These findings indicate that IKKalpha contributes to the tumor-promoting function of the TGFbeta-SMAD signaling pathway in particular cancers., PARP-1 dissociates Smad complexes from DNA by ADP-ribosylating Smad3 and Smad4, which attenuates Smad-specific gene responses and TGF-beta-induced epithelial-mesenchymal transition., study provides evidence SMAD3 gene, which encodes a key regulatory protein in transforming growth factor beta signalling pathway and is known to interact directly with BRCA2, may contribute to increased risk of breast cancer in BRCA2 mutation carriers, Data show that cyclin E-mediated inhibition of Smad3 is regulated by CDK2 phosphorylation of the Smad3 protein in MCF7 cells., Activation of peroxisome proliferator-activated receptor gamma (PPAR-gamma) inhibits transforming growth factor beta (TGF-beta)-induced epithelial-mesenchymal transition in lung cancer cells and prevents metastasis by antagonizing Smad3 function., SMAD3 mutations in the TGF-beta pathway cause a syndromic form of aortic aneurysms and dissections with early-onset osteoarthritis, Data show that the WWP2-N isoform interacts with Smad2 and Smad3, whereas WWP2-C interacts only with Smad7., Data demonstrate that RGC-32 interacts with Smad3 to mediate the epithelial-mesenchymal transition of human renal proximal tubular cells., TGFbeta1 induced MAD1 expression by recruitment C/EBPalpha/beta heterodimers, SP1, and SMAD3 binding to promoter of the MAD1., Activin A-ACVRIB/ALK4-Smad-dependent collagen production was augmented in SSc fibroblasts, suggesting the involvement of this signaling mechanism in systemic sclerosis., In malignant cells with a functional TGF-beta signalling pathway Rac1 antagonizes the TGF-beta1 growth inhibitory response and enhances cell migration by antagonistically regulating Smad2 and Smad3 activation, Identification of global targets and molecular pathways and networks associated with TGFbeta1/SMAD3 signaling allow for a better understanding of the mechanisms that determine epithelial cell phenotypes in fibrogenesis and carcinogenesis, l type-specific target selection by combinatorial binding of Smad2/3 proteins and hepatocyte nuclear factor 4alpha in HepG2 cells., In middle cerebral artery occlusion-induced activation of Smad-binding elements (SBEs), a downstream target of Smad 2/3 transcription factors regulates expression of the luciferase reporter., The causative mutation in a large family with autosomal dominant inheritance of thoracic aortic aneurysms leading to acute aortic dissections with intracranial and abdominal aortic aneurysms is identified by exome sequencing., TGF-beta1-induced activation of Smad3 is the critical step for the uPA upregulation and E-cadherin downregulation, HEB and E2A-bind the SCA motif at regions overlapping SMAD2/3 and FOXH1, in breast cancer cases SMAD3 was significantly over-expressed, we describe TGF-beta signalling through Smad2/3 and the importance of the linker region in the regulation and expression of genes induced by TGF-beta--{REVIEW}, the TRB3-SMAD3 interaction promoted the nuclear localization of SMAD3 because of the interaction of TRB3 with the MH2 domain of SMAD3, Androgen receptor transactivity is potentiated by TGF-beta1 through Smad3 but checked by its coactivator Hic-5/ARA55 in balding dermal papilla cells., USP15 is a deubiquitylating enzyme for receptor-activated SMAD3., Protein phosphatase PPM1A regulates the nuclear export of Smad2/3 through targeting nuclear exporter RanBP3., Study concludes that Smad3 regulates, at the transcriptional level, miR-200 family members, which themselves regulate ZEB1 and ZEB2, known transcriptional repressors of E-cadherin, at the posttranscriptional level in a TGF-beta-independent manner., we provide evidences that induction of TGF-beta1 production and Smad3 phosphorylation by Ox-LDL is mediated by Ras/ERK/PLTP pathway in human alveolar epithelial cells., Functional blockade of the voltage-gated potassium channel Kv1.3 mediates reversion of T effector to central memory lymphocytes through SMAD3/p21cip1 signaling., human umbilical cord blood-derived stromal cells which secrete a high level of TGF-beta1, modulate the Foxp3 expression of Treg cells through the TGF-beta1/Smad3 pathway to regulate graft-versus-host disease, Five novel SMAD3 mutations (one nonsense, two missense and two frame-shift mutations) were identified in five new aneurysms-osteoarthritis syndrome families, Enhanced TGF-beta1-induced Smad2 and -3 signaling in prostate cancer cells may correlate with tumor suppressive activity., Low Smad3 is associated with lung cancer., Smad3 and its phosphoisoforms are prognostic predictors of hepatocellular carcinoma after curative hepatectomy., Data suggest that TGF-beta, TGF-betaR1, TGF-betaR2, Smad4, pSmad2/3, and E-cadherin are closely related to tumor-node-metastasis (TNM) stage of colorectal cancer (CRC)., These findings suggest that Smad3 and Snail have circadian rhythm in vitro and vivo, and that circadian expression of Smad3 depends on CLOCK/BMAL1., When PI3K/Akt signaling is low, Wnt effectors are activated and function in conjunction with Smad2,3 to promote differentiation, Mechanical stretch stimulates Smad3-dependent CCN2 transcription on chromatin and COL1A1 expression in human inner meniscus cells., TGF-beta induces the formation of complexes comprising phosphorylated Smad1/5 and Smad3, which bind to BMP-responsive elements in vitro and in vivo and mediate TGF-beta-induced transcriptional repression., TGF-beta family signaling through Smads is conceptually a simple and linear signaling pathway, driven by sequential phosphorylation, with type II receptors activating type I receptors, which in turn activate R-Smads [review], AOS predisposes patients to aggressive and widespread cardiovascular disease and is associated with high mortality. Dissections can occur at relatively mildly increased aortic diameters., analysis of the dynamics of TGF-beta and Smad2/Smad3 signaling [review], We demonstrated in dermal fibroblasts that VEGF was overexpressed due to autocrine TGF-beta/Smad signaling in scleroderma., Zyxin is a transforming growth factor-beta (TGF-beta)/Smad3 target gene that regulates lung cancer cell motility via integrin alpha5beta1., neurogenesis is promoted by an interplay between the TGFbeta pathway, Smad3, and the H3K27me3 histone demethylase (HDM) JMJD3, Haploinsufficiency of SMAD3 leads to development of both thoracic aortic aneurysms and dissections., Dysregulated expression of TWIST1, TGF-beta1 and SMAD3 mRNA observed in osteoarthritis bone is reflected in the functionality of the osteoblast when these cells are cultured ex vivo., Different biologic responses to TGF-beta in the mammary epithelium are differentially affected by Smad3 dosage., CCL2/CCR2 chemokine signaling coordinates survival and motility of breast cancer cells through Smad3 protein- and p42/44 mitogen-activated protein kinase (MAPK)-dependent mechanisms., a differential regulation of Smads and TGF-beta receptors, TGFbeta and its downstream mediator Smad3 were both identfied as contributors to medulloblastoma metastasis and survival., results suggest that Smad3 linker phosphorylation has a negative regulatory role on Smad3 transcriptional activity and TGF-beta1/Smad3-induced renal epithelial-mesenchymal transition., Data indicate that dimethylfumarate and Ad-Nrf2 repressed TGF-beta-stimulated Smad3 activity by inhibiting Smad3 phosphorylation, which was restored by siRNA-mediated knockdown of Nrf2 expression., results demonstrate that HIF-1alpha transcription and protein synthesis are controlled by TGF-beta1/Smad3 signaling, whereas HIF-1alpha protein stability is controlled by PHD2, which is regulated by TGF-beta1/Smad3 signaling., The prevalence of SMAD4, SMAD2, and SMAD3 mutations in sporadic CRCs was 8.6% (64 of 744), 3.4% (25 of 744), and 4.3% (32 of 744), respectively., Smad3, pSmad3L(T179), and pSmad3L(S213) expression might be independent predictors of both shorter disease-free survival and shorter overall survival in gastric carcinoma patients after curative surgery., Genetic variation in the SMAD3 gene is involved in pathogenesis of both knee/hand osteoarthritis in Northeast Chinese population., findings indicate that miR-34b acts as a tumor metastasis suppressor through negatively modulating Smad3, which may provide a potential therapeutic strategy for pancreatic cancer, TGFbeta-stimulated Smad 3 acts as a key node to instill a feedback loop between deptor down-regulation and TORC1/2 activation in driving mesangial cell hypertrophy, ATP production by NaF promotes hypertrophy-like changes via activation of phospho-Smad1, SMAD2 and SMAD3 acetylatation by P300-CBP is mediated by TGFB1 in human lung cancer cells., results demonstrate the complex interplay between Smad3, p38alpha, and ERK1/2 signaling in the regulation of TIMP-3 gene expression in fibroblasts, which may play a role in inflammation, tissue repair, and fibrosis, a significant correlation between the NANOG expression and the expression of NODAL, P-SMAD3 or SNAIL, and the combination of NANOG and P-SMAD3 is a potential predictor of poor prognosis of HCC., SMAD3 mutations should be considered in patients of all ages with LDS-like phenotypes and negative TGFBR1/2 molecular tests, Notch4-dependent antagonism of canonical TGF-beta1 signaling defines unique temporal fluctuations of SMAD3 activity in proximal tubular epithelial cells exposed to shear stress., GM-CSF contributes to aortic aneurysms resulting from SMAD3 deficiency, SMAD3 was identified as a target of miR-145 in cystic fibrosis patients., Context-dependent responses to Smad2/3 imposed by Polycomb action provide a mechanism for selective gene regulation that can reconcile the apparently conflicting roles of this signaling pathway in pluripotency, differentiation, and reprogramming., Nuclear expressions of Smad3 and Smad4 were related to prognosis of clear cell renal cell carcinoma patients and may serve as novel prognostic markers in clear cell renal cell carcinoma patients., These findings for the first time define H2O2 as a signaling molecule that modulate Smad3 linker phosphorylation., Smad3 reversed the effects of TGF-beta1-induced osteoclast formation in the co-culture system., TGF-beta enhances IL-21-induced differentiation of human IL-21-producing CD4+ T cells via Smad3., a nuclear envelope-localized mechanism of inactivating TGF-beta signaling in which MAN1 competes with transcription factors for binding to Smad2 and Smad3 and facilitates their dephosphorylation by PPM1A., a detailed computational model for TGF-beta signalling that incorporates elements of previous models together with crosstalking between Smad1/5/8 and Smad2/3 channels through a negative feedback loop dependent on Smad7., These findings indicate crosstalk between p38 and smad3 through TGF-beta1 in choriocarcinoma cells., the study reports SMAD3 mutations in oral carcinoma., Transforming growth factor-beta(1) represses bone morphogenetic protein 4-mediated Smad signaling in pulmonary artery smooth muscle cells via Smad3., Protumorigenic actions of S100A2 involve regulation of PI3/Akt signaling and functional interaction with Smad3., findings indicate that ERK5 plays a critical role in TGF-beta1-induced pulmonary fibrosis via enhancing Smad3 acetylation., inhibition of Smad2/3 by siRNA significantly decreased the production of IL-6 and VEGF in mesenchymal stem cells and induced their osteogenic differentiation, SMAD3 rs17228212 gene variant is associated with lower risk of CVA., This is the first study to provide evidence of new and differential roles for NFAT3 and SMAD3 in the osteoarthritis process in the regulation of miR-140 transcription, Study is consistent with a key role for KCa3.1 renal proximal tubular cells in mediating the TGF-beta1 induction of MCP-1 expression in HK2 cells via Smad3, p38 and ERK1/2 MAPK signaling pathways., ZNF451 acts as a transcriptional corepressor for Smad3/4 and negatively regulates TGF-beta signaling., WWOX modulates SMAD3 signaling in breast cells via direct WW-domain mediated binding and potential cytoplasmic sequestration of SMAD3 protein., Glucocorticoids recruit Tgfbr3 and Smad1 to shift transforming growth factor-beta signaling from the Tgfbr1/Smad2/3 axis to the Acvrl1/Smad1 axis in lung fibroblasts., Nodal expression was significantly upregulated in glioma cells when TGF-beta was added, whereas the TGF-beta-induced Nodal expression was evidently inhibited by transfection Smad2 or Smad3 siRNAs., Data indicate that decrease in hepatitis B virus (HBV)-DNA restored pSmad3C signalling in hepatocytes, while eliminating prior fibrocarcinogenic pSmad3L signalling., Smad3 plays an important role in the TGF-beta/Smad3 signaling pathway., FOXM1 promotes breast cancer metastasis by increasing nuclear retention of SMAD3; there is crosstalk between FOXM1 and TGF-beta/SMAD3 pathways, The molecular interactions of FOXL2, GATA4, and SMAD3 and their roles in the regulation of CCND2 using co-immunoprecipitation, promoter transactivation, and cell viability assays in human granulosa cell tumor cells, were investigated., +58CpG methylation may be one of the mechanisms accounting for reduced recruitment of the transcriptional activator AhR to DCN 5'-UTR, and suggest that this mechanism promotes TGF-beta/Smad signaling by enhancing the phosphorylation of Smad3, High expression of IGFBP7 in fibroblasts induced by colorectal cancer cells is co-regulated by TGF-beta and Wnt signaling in a Smad2/3-Dvl2/3-dependent manner., SNPs associated with increased risk of repeat operation and shorter time to repeat surgery for Crohn's disease, Using a human CTL system model based on a CD8(+)/CD103(-) T cell clone specific of a lung tumor-associated Ag, we demonstrated that the transcription factors Smad2/3 and NFAT-1 are two critical regulators of this process., our study identifies phosphorylation of T388 in the Smad3 MH2 domain as an important mechanism that regulates the profibrotic TGF-beta/Smad3 signaling pathway, Galectin-1 stimulates motility of human umbilical cord blood-derived mesenchymal stem cells by downregulation of smad2/3-dependent COL3A1/COL5A1 and upregulation of NF-kappaB-dependent fibronectin/laminin 5 expression., Serum TGF-beta1 and SMAD3 levels are closely associated with coronary artery disease, and may become useful biomarkers for diagnosis and risk stratification., Restoration of TbetaRII and SMAD3 together, but not separately, reinstates TGF-beta signaling and increases CTGF/CCN2 and type I collagen levels., Interleukin-6 (IL-6) trans signaling drives a STAT3-dependent pathway that leads to hyperactive transforming growth factor-beta (TGF-beta) signaling promoting SMAD3 activation and fibrosis via Gremlin protein., SMAD3 is subject to cis-acting regulatory polymorphism in the tissues of both primary osteoarthritis and the aneurysms-osteoarthritis syndrome., A positive feedback loop between miR-26a and p-Smad3 is involved in lung fibrosis., Reveal an opposite role of Hsp70 and Hsp90 in regulating TGF-beta signaling by implicating CHIP-mediated Smad3 ubiquitination and degradation. This study provides a new insight into understanding the regulation of the TGF-beta signaling by chaperones., These studies highlight the role of free radicals in p53 activation and subsequent pro-fibrotic reprogramming by TGF-beta1 via the SMAD3-p53 transcriptional axis., our data suggest that PTTG1 promotes the proliferation of prostate cancer cells via the inhibition of SMAD3. SMAD3 thus appears to be a novel therapeutic target for suppressing the growth of prostate cancer., Smad3 and phospho-Smad3 protein levels gradually decreased while TGF-beta1 mRNA level gradually decreased and the Smad7 mRNA level gradually increased from normal anterior pituitaries, noninvasive NFPAs, to invasive NFPAs., acetaldehyde up-regulates COL1A2 by modulating the role of Ski and the expression of SMADs 3, 4, and 7., Nodal promotes the self-renewal of human colon cancer stem cells and mediate carcinogenesis of human colorectal cancer via an autocrine manner through Smad2/3 pathway., Gene-expression profiling of 12 PDAC xenografts was performed, and SMAD3 was identified as an EMT-related gene. Showed that SMAD3 accumulated in the nuclei of tumor cells, but was not detected in most epithelial cells in the pancreatic duct., SMAD3 mutations described as a cause of thoracic aortic aneurysms and aortic dissections, in the setting of premature osteoarthritis and associated with aggressive form of vasculopathy with cerebrovascular involvement and infantile aortic disease, Data suggest that extracellular signal-regulated kinases ERK1/2 signaling can cross-interact with the transforming growth factor beta2/Smad2/3 and the Jagged-1/Notch-3 signaling in retinal pigment epithelium cells epithelial-mesenchymal transition., SMAD3 gene mutations are associated with aortic dilatation and osteoarthritis, but also autoimmunity and peripheral neuropathy which mimics type II Charcot-Marie-Tooth., SMAD3 is significantly associated with the total burden of radiographic OA. Further studies are required to reveal the mechanism of the association, The current findings indicate miR-146a plays an important role in skeletogenesis through attenuation of SMAD2 and SMAD3 function., Smad2 and Smad3 are both necessary for the formation of posterior capsular opacification of human lens epithelial cells., SMAD3 regulates transcription of MuRF-1 by increasing FoxO3 binding at a conserved FRE-SBE motif within the proximal promoter region, and by increasing FoxO3 protein content and transcriptional activity., In conclusion, this study identifies opposing roles for Smad2 and Smad3 in peritoneal dialysis-associated peritoneal fibrosis, glycated collagen in the cardiac interstitium triggers an autocrine TGF-beta2 signaling pathway that stimulates alpha11 integrin expression through Smad2/3 binding elements in the alpha11 integrin promoter, Smad3 promotes the proliferation and steroidogenesis of human ovarian luteinized granulosa cells, and these effects may be mediated by the FSHR/LHR-PKA signaling pathway., Data indicate that overexpression of SMAD3 protein in PC3 cells (PC3-SMAD3) significantly increased the phosphorylated form of SMAD3., Smad3 binds to chromatin together with TTF-1, but not with Smad4, at some Smad3-binding regions when TGF-beta signaling is absent, and knockdown of Smad4 expression does not attenuate Smad3 binding in these regions., in human HCC tissues, SPTBN1 expression correlated negatively with expression levels of STAT3, ATF3, and CREB2; SMAD3 expression correlated negatively with STAT3 expression, Activin A, B, and AB produce comparable increases in human trophoblast cell invasion by up-regulating N-cadherin expression in a SMAD2/3-SMAD4-dependent manner., PREP1 modulates the cellular sensitivity to TGF-beta by inducing the small mothers against decapentaplegic homolog 3 (SMAD3) nuclear translocation., Mechanical compression upregulates MMP9 through SMAD3 but not SMAD2 modulation in hypertrophic scar fibroblasts., Arsenic trioxide blocked hepatocellular carcinoma angiogenesis by miR-491-mediated inhibition of TGF-b/SMADs/NF-kB signal pathway., miR-136 may play a tumor-suppressive role by repressing EMT and prometastatic traits via targeting Smad2 and Smad3., Our results demonstrate a critical role of the counterbalance between the Smad3 C-tail and linker phosphorylation in tumorigenesis and metastasis, The expression levels of collagens type I/III, TGF-beta1, Smad2/3/4/7 and PAI-1 (plasminogen activator inhibitor type 1) in gluteal muscle contraction (GMC) patients were measured., Immunostaining of total SMAD3 was reduced in the endometriosis group, but the localization of pSMAD3 was not altered., Smad3 expression was found to be predictive of prognosis in esophageal squamous cell carcinoma., Lefty reduced the levels of phosphorylated Smad2, Smad3, and ERK1/2, inhibited the proliferation and invasion of glioma cells, and increased their apoptosis., knockdown of Smad3 significantly reduced TGF-beta1-induced Col.I production. These findings were further evident by the results that overexpression of Smad2 attenuated the expression of Col.I and TIMP-1, Smad3/4 is a novel drug sensitivity regulator in TGFbeta-mediated chemotherapy-resistant colorectal cancer cells., genetic polymorphisms may be associated with the susceptibility to rheumatoid arthritis in the Polish population, Global gene expression profiling identifies ALDH2, CCNE1 and SMAD3 as potential prognostic markers in upper tract urothelial carcinoma., Data indicate that Smad3 protein played a major role in the induction of fibrogenic genes by TGFbeta1 in hepatic stellate cells LX-2., Ca2+- and KCa3.1-dependent processes facilitate "constitutive" alpha smooth muscle actin expression and Smad2/3 signalling in IPF-derived fibroblasts, and thus promote fibroblast to myofibroblast differentiation., Together, our findings defined an essential role for the KMT1E/SMAD2/3 repressor complex in TGFbeta-mediated lung cancer metastasis., DRAK1 was predominantly localized in the cytoplasm and bound to Smad3, thereby interrupting Smad3/Smad4 complex formation, which is the core process for the induction of tumor suppressor genes by TGF-beta1, SMAD3 expression was up-regulated in colorectal neoplasms., Nodal induces signal transduction through the Smad2/3-dependent pathway in vitro. Results that Nodal promotes pancreatic cancer cell migration and invasion and induces epithelial-mesenchymal transition., Mesothelioma cells promote migration and invasive growth by switching activin signaling from canonical Smad3 pathway to non-canonical ERK pathway signaling., our findings indicate that miR-145 is a tumour suppressor that affects invasive and metastatic properties of NPC via the miR-145/Smad3 axis, leading us to propose that miR-145 overexpression might be a potential therapeutic strategy of NPC intervention., TGF-beta/Smad2/Smad3 signal pathway is involved in glioma tumor cells proliferation and apoptosis., Elf5 inhibits TGF-Beta-driven epithelial mesenchymal transition via repressing SMAD3 phosphorylation in prostate cancer cells., MDA-MB-231 cells displaying Smad3 activity moved faster., An association of SNP in SMAD3 with temporomandibular joint osteoarthritis in female Han Chinese., PTEN loss initiates tubular dysfunction via SMAD3- and p53-mediated fibrotic gene induction, with accompanying PAI-1-dependent proliferative arrest, and cooperates with TGFbeta1 to induce the expression of profibrotic genes and tubular apoptosis., our findings suggest that Ski represses TGF-b-induced EMT and invasion by inhibiting SMAD-dependent signaling in non-small cell lung cancer.Ski-silenced and overexpressed A549 cells showed an increase and a reduction in the SMAD3 phosphorylation level, These findings uncover a plausible mechanism for NF-kappaB-sustained TGF-beta/Smad activation via miR-148a in glioblastoma., High Smad3 expression is associated with renal fibrosis in lupus nephritis., Neovibsanin B utilizes the canonical Smad signalling pathway to stimulate ECM synthesis in human optic nerve head cells., hCLP46 increases Smad3 protein stability via inhibiting its ubiquitin-proteasomal degradation, Gene-gene interactions between Smad3 rs6494629T/C and TIMP3 rs715572G/A polymorphisms may play more important protective roles in knee OA., SMAD3 and AKT phosphorylation was enhanced during the culture of human SSCs, The Single Nucleotide Polymorphism rs2289263 in the SMAD3 gene is associated with ventricular septal defects in Chinese Han populations., Smad3 was a direct and functional target of miR-23b in heat-denatured fibroblasts., PCDH1 and SMAD3 act in a single pathway in asthma susceptibility that affects sensitivity of the airway epithelium to TGF-beta., Our finding expands the mutation spectrum of SMAD3 gene and further strengthens the connection between the presence of aneurysms-osteoarthritis phenotype and SMAD3 mutations, The results suggested a novel function for Twist in the promotion of EMT via TGF-b/Smad3 signaling pathway. Thus, Twist constitutes a potential therapeutic target in human cervical cancer., Astragaloside can delay the renal fibrosis process in diabetic mice by influencing the TGF-beta/SMADS signaling pathway and down-regulating TGF-beta1, SMAD2/3, and alpha-SMA expression., CC and CT+TT and TT and TG+GG genotypes of SMAD3 rs12102171 and rs2289263 polymorphisms together with BMI may be susceptible factors for osteoarthritis., Suggest that TGF-beta1/Smad and Wnt/CTNNB1 signaling pathways both contribute to pathological scar formation., Different signaling pathways are involved in osteitis in CRS and are activated by the TGF-beta/Smad signaling pathway in CRSwNP versus the TGF-beta/Smad-independent signaling pathway in CRSsNP., SMAD3 is a necessary factor for TGFbeta-mediated stimulation of mRNA and protein expression of type IV collagen genes in human vascular smooth muscle cells; it regulates expression of COL4a1 and COL4a2, results indicate that miR-16-5p is an important regulator of SMAD3 expression in human chondrocytes and may contribute to the development of osteoarthritis, Follistatin-like 1 attenuates differentiation and survival of erythroid cells through Smad2/3 signaling., EAF2 binding does not alter Smad3 phosphorylation but causes Smad3 cytoplasmic retention, competes with Smad4 for binding to Smad3, and prevents p300-Smad3 complex formation, Up-regulation of smad3 is associated with endometrial cancer., Data show that the expression of transforming growth factor beta 1 (TGFB1) was correlated with the expression of SMA- and MAD-related protein 3 (SMAD3) and matrix metalloproteinase-13 (MMP13) in osteoarthritis (OA)-affected cartilage., HoxB7 is associated with tumor metastasis in patients with lung adenocarcinoma and HoxB7 may be implicated in promoting the development of lung adenocarcinoma through activation of the TGF-beta/SMAD3 signaling., TGF-beta/Smad signalling pathway and VEGF-A participate in the pathogenesis of sarcoidosis., Induction of pSmad3L through BLT1-NOX-ROS-EGFR-PI3K-ERK1/2 signaling pathway is a key mechanism by which LTB4 blocks the anti-proliferative responses of TGF-beta1 in breast tumors., Data suggest SHC1 (SH2 domain protein C1) expression down-regulates epithelial-mesenchymal transition by repressing TGFB-induced SMAD2/3 activation through differential partitioning of receptors at cell surface of mammocytes/keratinocytes., These results for the first time demonstrate a role of Cdk5/p35 in the regulation of cell cycle progression modulated by TGF-beta1.,
OMIM_DISEASE Loeys-Dietz syndrome 3,
SP_COMMENT disease:Defects in SMAD3 may be a cause of colorectal cancer (CRC) [MIM:114500]., domain:The MH2 domain is sufficient to carry protein nuclear export., function:Transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinase. SMAD3 is a receptor-regulated SMAD (R-SMAD)., PTM:Phosphorylated on serine by TGF-beta and activin type 1 receptor kinases., similarity:Belongs to the dwarfin/SMAD family., similarity:Contains 1 MH1 (MAD homology 1) domain., similarity:Contains 1 MH2 (MAD homology 2) domain., subcellular location:In the cytoplasm in the absence of ligand. Migration to the nucleus when complexed with Smad4., subunit:Interacts with HGS. Interacts with NEDD4L in response to TGF-beta. Interacts with TTRAP (By similarity). Interacts with SARA (SMAD anchor for receptor activation); form trimers with another SMAD3 and the co-SMAD SMAD4. Interacts with JUN/FOS, vitamin D receptor, homeobox protein TGIF and TGIF2, PEBP2-alpha C subunit, CREB-binding protein (CBP), p300, SKI, SNON, ATF2, SMURF2, AIP1, DACH1 and TGFB1I1. Part of a complex consisting of AIP1, ACVR2A, ACVR1B and SMAD3. Found in a complex with SMAD2 and TRIM33 upon addition of TGF-beta. Interacts with SMAD2 and TRIM33. Found in a complex with SMAD3, Ran and XPO4. Interacts with XPO4. Interacts with LBXCOR1 and CORL2.,