Gene Symbol: Smad2
Description: SMAD family member 2
Alias: JV18, JV18-1, MADH2, MADR2, hMAD-2, hSMAD2, mothers against decapentaplegic homolog 2, MAD homolog 2, SMAD, mothers against DPP homolog 2, Sma- and Mad-related protein 2, mother against DPP homolog 2
Species: human
Products:     Smad2

Top Publications

  1. Massague J. TGF-beta signal transduction. Annu Rev Biochem. 1998;67:753-91 pubmed
    ..Mutations in these pathways are the cause of various forms of human cancer and developmental disorders. ..
  2. He W, Dorn D, Erdjument Bromage H, Tempst P, Moore M, Massague J. Hematopoiesis controlled by distinct TIF1gamma and Smad4 branches of the TGFbeta pathway. Cell. 2006;125:929-41 pubmed
    ..nuclear protein Transcriptional Intermediary Factor 1gamma (TIF1gamma) selectively binds receptor-phosphorylated Smad2/3 in competition with Smad4...
  3. Nakano A, Koinuma D, Miyazawa K, Uchida T, Saitoh M, Kawabata M, et al. Pin1 down-regulates transforming growth factor-beta (TGF-beta) signaling by inducing degradation of Smad proteins. J Biol Chem. 2009;284:6109-15 pubmed publisher
    ..Pin1 interacted with Smad2 and Smad3 but not Smad4; this interaction was enhanced by the phosphorylation of (S/T)P motifs in the Smad linker ..
  4. Lin X, Liang M, Feng X. Smurf2 is a ubiquitin E3 ligase mediating proteasome-dependent degradation of Smad2 in transforming growth factor-beta signaling. J Biol Chem. 2000;275:36818-22 pubmed, we have identified a novel HECT class ubiquitin E3 ligase, designated Smurf2, that negatively regulates Smad2 signaling...
  5. Liberati N, Datto M, Frederick J, Shen X, Wong C, Rougier Chapman E, et al. Smads bind directly to the Jun family of AP-1 transcription factors. Proc Natl Acad Sci U S A. 1999;96:4844-9 pubmed
    ..Together, these data suggest that TGFbeta-mediated transcriptional activation through AP-1 sites may involve a regulated interaction between Smads and AP-1 transcription factors. ..
  6. Abdollah S, Macias Silva M, Tsukazaki T, Hayashi H, Attisano L, Wrana J. TbetaRI phosphorylation of Smad2 on Ser465 and Ser467 is required for Smad2-Smad4 complex formation and signaling. J Biol Chem. 1997;272:27678-85 pubmed
    ..Recently, it was demonstrated that Smad2 interacts transiently with and is a direct substrate of the transforming growth factor-beta (TGF-beta) type I ..
  7. Yamagata H, Matsuzaki K, Mori S, Yoshida K, Tahashi Y, Furukawa F, et al. Acceleration of Smad2 and Smad3 phosphorylation via c-Jun NH(2)-terminal kinase during human colorectal carcinogenesis. Cancer Res. 2005;65:157-65 pubmed
    ..TGF-beta signaling involves Smad2/3 phosphorylated at linker regions (pSmad2/3L) and COOH-terminal regions (pSmad2/3C)...
  8. Shinto O, Yashiro M, Toyokawa T, Nishii T, Kaizaki R, Matsuzaki T, et al. Phosphorylated smad2 in advanced stage gastric carcinoma. BMC Cancer. 2010;10:652 pubmed publisher a critical integrator of TGF? receptor signaling transduction systems, not much is known about the role of Smad2 expression in gastric carcinoma...
  9. Kretzschmar M, Doody J, Timokhina I, Massague J. A mechanism of repression of TGFbeta/ Smad signaling by oncogenic Ras. Genes Dev. 1999;13:804-16 pubmed
    ..Ras inhibits TGFbeta signaling in mammary and lung epithelial cells by negatively regulating the TGFbeta mediators Smad2 and Smad3...

More Information


  1. Wotton D, Lo R, Lee S, Massague J. A Smad transcriptional corepressor. Cell. 1999;97:29-39 pubmed
    Following TGFbeta receptor-mediated phosphorylation and association with Smad4, Smad2 moves into the nucleus, binds to target promoters in association with DNA-binding cofactors, and recruits coactivators such as p300/CBP to activate ..
  2. Qiu W, Schönleben F, Li X, Su G. Disruption of transforming growth factor beta-Smad signaling pathway in head and neck squamous cell carcinoma as evidenced by mutations of SMAD2 and SMAD4. Cancer Lett. 2007;245:163-70 pubmed
    ..of the TGF-beta -Smad signaling pathway, TGF-beta type I receptor (TGFBRI), TGF-beta type II receptor (TGFBRII), SMAD2, SMAD3 and SMAD4, in eight human head and neck squamous cell carcinoma (HNSCC) cell lines...
  3. Zhang Y, Feng X, Derynck R. Smad3 and Smad4 cooperate with c-Jun/c-Fos to mediate TGF-beta-induced transcription. Nature. 1998;394:909-13 pubmed
    ..This mechanism of transcriptional activation by TGF-beta, through functional and physical interactions between Smad3-Smad4 and c-Jun-c-Fos, shows that Smad signalling and MAPK/JNK signalling converge at AP1-binding promoter sites. ..
  4. Xu L, Kang Y, Cöl S, Massague J. Smad2 nucleocytoplasmic shuttling by nucleoporins CAN/Nup214 and Nup153 feeds TGFbeta signaling complexes in the cytoplasm and nucleus. Mol Cell. 2002;10:271-82 pubmed
    The transcription factor Smad2 is released from cytoplasmic retention by TGFbeta receptor-mediated phosphorylation, accumulating in the nucleus where it associates with cofactors to regulate transcription...
  5. Cordenonsi M, Dupont S, Maretto S, Insinga A, Imbriano C, Piccolo S. Links between tumor suppressors: p53 is required for TGF-beta gene responses by cooperating with Smads. Cell. 2003;113:301-14 pubmed
    ..p53 can physically interact in vivo with Smad2 in a TGF-beta-dependent fashion...
  6. Nakao A, Imamura T, Souchelnytskyi S, Kawabata M, Ishisaki A, Oeda E, et al. TGF-beta receptor-mediated signalling through Smad2, Smad3 and Smad4. EMBO J. 1997;16:5353-62 pubmed
    ..b>Smad2 and Smad3 are structurally highly similar and mediate TGF-beta signals...
  7. Long J, Matsuura I, He D, Wang G, Shuai K, Liu F. Repression of Smad transcriptional activity by PIASy, an inhibitor of activated STAT. Proc Natl Acad Sci U S A. 2003;100:9791-6 pubmed
    ..Taken together, our studies indicate that PIASy can inhibit TGF-beta/Smad transcriptional responses through interactions with Smad proteins and HDAC. ..
  8. Luo K, Stroschein S, Wang W, Chen D, Martens E, Zhou S, et al. The Ski oncoprotein interacts with the Smad proteins to repress TGFbeta signaling. Genes Dev. 1999;13:2196-206 pubmed
    ..On phosphorylation and activation by the active TGFbeta receptor complex, Smad2 and Smad3 form hetero-oligomers with Smad4 and translocate into the nucleus, where they interact with different ..
  9. Mavrakis K, Andrew R, Lee K, Petropoulou C, Dixon J, Navaratnam N, et al. Arkadia enhances Nodal/TGF-beta signaling by coupling phospho-Smad2/3 activity and turnover. PLoS Biol. 2007;5:e67 pubmed
    ..Loss of Arkadia in embryonic cells causes nuclear accumulation of phospho-Smad2/3 (P-Smad2/3), the effectors of Nodal signaling; however, these must be repressed or hypoactive as the expression ..
  10. Itoh S, Ericsson J, Nishikawa J, Heldin C, ten Dijke P. The transcriptional co-activator P/CAF potentiates TGF-beta/Smad signaling. Nucleic Acids Res. 2000;28:4291-8 pubmed
    ..TGF-beta-mediated activation of TGF-beta type I receptor stimulates the phosphorylation of Smad2 and Smad3 and subsequent heteromeric complex formation with Smad4...
  11. Akiyoshi S, Inoue H, Hanai J, Kusanagi K, Nemoto N, Miyazono K, et al. c-Ski acts as a transcriptional co-repressor in transforming growth factor-beta signaling through interaction with smads. J Biol Chem. 1999;274:35269-77 pubmed
    ..Among them, Smads 2 and 3 are activated specifically by TGF-beta. We identified c-Ski as a Smad2 interacting protein...
  12. Lagna G, Hata A, Hemmati Brivanlou A, Massague J. Partnership between DPC4 and SMAD proteins in TGF-beta signalling pathways. Nature. 1996;383:832-6 pubmed
    ..Smad1 and Smad2 have been shown to mimic the effects of BMP and activin, respectively, both in Xenopus and in mammalian cells, ..
  13. Komuro A, Imamura T, Saitoh M, Yoshida Y, Yamori T, Miyazono K, et al. Negative regulation of transforming growth factor-beta (TGF-beta) signaling by WW domain-containing protein 1 (WWP1). Oncogene. 2004;23:6914-23 pubmed
    ..Consistent with these results, WWP1 inhibited phosphorylation of Smad2 induced by TGF-beta. WWP1 thus negatively regulates TGF-beta signaling in cooperation with Smad7...
  14. Feng X, Liang Y, Liang M, Zhai W, Lin X. Direct interaction of c-Myc with Smad2 and Smad3 to inhibit TGF-beta-mediated induction of the CDK inhibitor p15(Ink4B). Mol Cell. 2002;9:133-43 pubmed
    ..In this study, we reveal that c-Myc physically interacts with Smad2 and Smad3, two specific signal transducers involved in TGF-beta signaling...
  15. Kalinina N, Agrotis A, Antropova Y, Ilyinskaya O, Smirnov V, Tararak E, et al. Smad expression in human atherosclerotic lesions: evidence for impaired TGF-beta/Smad signaling in smooth muscle cells of fibrofatty lesions. Arterioscler Thromb Vasc Biol. 2004;24:1391-6 pubmed
    ..b>Smad2, Smad3, and Smad4 proteins are signaling molecules by which TGF-beta modulates gene transcription...
  16. Fleming N, Jorissen R, Mouradov D, Christie M, Sakthianandeswaren A, Palmieri M, et al. SMAD2, SMAD3 and SMAD4 mutations in colorectal cancer. Cancer Res. 2013;73:725-35 pubmed publisher
    ..frequently harbor somatic mutations in the pathway members TGFBR2 and SMAD4, but to what extent mutations in SMAD2 or SMAD3 contribute to tumorigenesis is unclear...
  17. Petersen M, Pardali E, van der Horst G, Cheung H, van den Hoogen C, van der Pluijm G, et al. Smad2 and Smad3 have opposing roles in breast cancer bone metastasis by differentially affecting tumor angiogenesis. Oncogene. 2010;29:1351-61 pubmed publisher
    ..How TGF-beta elicits these dichotomous functions and which roles the principle intracellular effector proteins Smad2 and Smad3 have therein, is unclear...
  18. Alarcon C, Zaromytidou A, Xi Q, Gao S, Yu J, Fujisawa S, et al. Nuclear CDKs drive Smad transcriptional activation and turnover in BMP and TGF-beta pathways. Cell. 2009;139:757-69 pubmed publisher
    ..Thus, nuclear CDK8/9 drive a cycle of Smad utilization and disposal that is an integral part of canonical BMP and TGF-beta pathways. ..
  19. Tian Y, Wu P, Luo A, Xi L, Zhou J, Ma D. [Expression and significance of Smad2/3 and HPV16 E7 in cervical intraepithelial neoplasia and cervical carcinoma]. Ai Zheng. 2007;26:967-71 pubmed
    ..This study was to detect the expression of Smad2/3 and HPV16 E7 protein in different cervical lesions, and to explore their possible roles in tumor genesis and ..
  20. Luciakova K, Kollarovic G, Barath P, Nelson B. Growth-dependent repression of human adenine nucleotide translocator-2 (ANT2) transcription: evidence for the participation of Smad and Sp family proteins in the NF1-dependent repressor complex. Biochem J. 2008;412:123-30 pubmed publisher
    ..These findings suggest a possible functional relationship between the NF1 and Smad proteins that has not been previously observed. ..
  21. Kim K, Wei Y, Szekeres C, Kugler M, Wolters P, Hill M, et al. Epithelial cell alpha3beta1 integrin links beta-catenin and Smad signaling to promote myofibroblast formation and pulmonary fibrosis. J Clin Invest. 2009;119:213-24 pubmed publisher
    ..These findings demonstrate epithelial integrin-dependent profibrotic crosstalk between beta-catenin and Smad signaling and support the hypothesis that EMT is an important contributor to pathologic fibrosis. ..
  22. Fukuchi M, Imamura T, Chiba T, Ebisawa T, Kawabata M, Tanaka K, et al. Ligand-dependent degradation of Smad3 by a ubiquitin ligase complex of ROC1 and associated proteins. Mol Biol Cell. 2001;12:1431-43 pubmed
    ..Smad3 bound to ROC1-SCF(Fbw1a) is then exported from the nucleus to the cytoplasm for proteasomal degradation. TGF-beta/Smad3 signaling is thus irreversibly terminated by the ubiquitin-proteasome pathway. ..
  23. Tsukazaki T, Chiang T, Davison A, Attisano L, Wrana J. SARA, a FYVE domain protein that recruits Smad2 to the TGFbeta receptor. Cell. 1998;95:779-91 pubmed
    ..We now identify SARA (for Smad anchor for receptor activation), a FYVE domain protein that interacts directly with Smad2 and Smad3...
  24. Liu X, Elia A, Law S, Golemis E, Farley J, Wang T. A novel ability of Smad3 to regulate proteasomal degradation of a Cas family member HEF1. EMBO J. 2000;19:6759-69 pubmed
    ..These data provide the first evidence for a novel cytoplasmic activity of Smad3 in regulating proteasomal degradation of HEF1 and also suggest a role for HEF1 in a negative feedback mechanism of the TGF-ss signaling pathway. ..
  25. Quinn Z, Yang C, Wrana J, McDermott J. Smad proteins function as co-modulators for MEF2 transcriptional regulatory proteins. Nucleic Acids Res. 2001;29:732-42 pubmed
    ..Our studies indicate that Smad2 and 4 (Smad2/4) complexes cooperate with MEF2 regulatory proteins in a GAL4-based one-hybrid reporter gene assay...
  26. Hata A, Lo R, Wotton D, Lagna G, Massague J. Mutations increasing autoinhibition inactivate tumour suppressors Smad2 and Smad4. Nature. 1997;388:82-7 pubmed
    b>Smad2 and Smad4 are related tumour-suppressor proteins, which, when stimulated by the growth factor TGF-beta, form a complex to inhibit growth...
  27. Zhang Y, Chang C, Gehling D, Hemmati Brivanlou A, Derynck R. Regulation of Smad degradation and activity by Smurf2, an E3 ubiquitin ligase. Proc Natl Acad Sci U S A. 2001;98:974-9 pubmed
    ..At higher expression levels, Smurf2 also decreases the protein levels of Smad2, but not Smad3...
  28. Furumatsu T, Tsuda M, Taniguchi N, Tajima Y, Asahara H. Smad3 induces chondrogenesis through the activation of SOX9 via CREB-binding protein/p300 recruitment. J Biol Chem. 2005;280:8343-50 pubmed
    ..In the present study, we investigated the relationship between TGF-beta-dependent Smad2/3 signaling pathways and the SOX9-CBP/p300 transcriptional complex at the early stage of chondrogenesis...
  29. Kamaraju A, Roberts A. Role of Rho/ROCK and p38 MAP kinase pathways in transforming growth factor-beta-mediated Smad-dependent growth inhibition of human breast carcinoma cells in vivo. J Biol Chem. 2005;280:1024-36 pubmed
    ..a human breast cancer cell line MCF10CA1h and demonstrate that p38 MAP kinase and Rho/ROCK pathways together with Smad2 and Smad3 are necessary for TGF-beta-mediated growth inhibition of this cell line...
  30. Long J, Wang G, Matsuura I, He D, Liu F. Activation of Smad transcriptional activity by protein inhibitor of activated STAT3 (PIAS3). Proc Natl Acad Sci U S A. 2004;101:99-104 pubmed
    ..Taken together, our studies indicate that on TGF-beta treatment, PIAS3 can form a complex with Smads and p300/CBP and activate Smad transcriptional activity. ..
  31. Nishihara A, Hanai J, Imamura T, Miyazono K, Kawabata M. E1A inhibits transforming growth factor-beta signaling through binding to Smad proteins. J Biol Chem. 1999;274:28716-23 pubmed
    ..We found that E1A interacts specifically with receptor-regulated Smads, suggesting a novel mechanism whereby E1A antagonizes TGF-beta signaling...
  32. Shi X, Bai S, Li L, Cao X. Hoxa-9 represses transforming growth factor-beta-induced osteopontin gene transcription. J Biol Chem. 2001;276:850-5 pubmed
    b>Smad2 and Smad3 are downstream transforming growth factor-beta (TGF-beta) signaling molecules...
  33. Kim R, Wang D, Tsang M, Martin J, Huff C, de Caestecker M, et al. A novel smad nuclear interacting protein, SNIP1, suppresses p300-dependent TGF-beta signal transduction. Genes Dev. 2000;14:1605-16 pubmed
    ..The carboxyl terminus of SNIP1 interacts with Smad1 and Smad2 in yeast two-hybrid as well as in mammalian overexpression systems...
  34. Matsuura I, Denissova N, Wang G, He D, Long J, Liu F. Cyclin-dependent kinases regulate the antiproliferative function of Smads. Nature. 2004;430:226-31 pubmed
    ..Because cancer cells often contain high levels of CDK activity, diminishing Smad3 activity by CDK phosphorylation may contribute to tumorigenesis and TGF-beta resistance in cancers. ..
  35. Mori S, Matsuzaki K, Yoshida K, Furukawa F, Tahashi Y, Yamagata H, et al. TGF-beta and HGF transmit the signals through JNK-dependent Smad2/3 phosphorylation at the linker regions. Oncogene. 2004;23:7416-29 pubmed
    ..In conclusion, HGF and TGF-beta transmit the signals through JNK-mediated R-Smads phosphorylation at linker regions. ..
  36. Lo R, Massague J. Ubiquitin-dependent degradation of TGF-beta-activated smad2. Nat Cell Biol. 1999;1:472-8 pubmed
    ..Here we investigate the fate of activated Smad2. We show that receptor-mediated activation leads to multi-ubiquitination and subsequent degradation of Smad2 by ..
  37. Lin X, Duan X, Liang Y, Su Y, Wrighton K, Long J, et al. PPM1A functions as a Smad phosphatase to terminate TGFbeta signaling. Cell. 2006;125:915-28 pubmed
    ..PPM1A dephosphorylates and promotes nuclear export of TGFbeta-activated Smad2/3...
  38. Kalo E, Buganim Y, Shapira K, Besserglick H, Goldfinger N, Weisz L, et al. Mutant p53 attenuates the SMAD-dependent transforming growth factor beta1 (TGF-beta1) signaling pathway by repressing the expression of TGF-beta receptor type II. Mol Cell Biol. 2007;27:8228-42 pubmed
    ..We found that 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 ..
  39. Eppert K, Scherer S, Ozcelik H, Pirone R, Hoodless P, Kim H, et al. MADR2 maps to 18q21 and encodes a TGFbeta-regulated MAD-related protein that is functionally mutated in colorectal carcinoma. Cell. 1996;86:543-52 pubmed
    ..We demonstrate that MADR2 is specifically regulated by TGFbeta and not bone morphogenetic proteins...
  40. Koinuma D, Tsutsumi S, Kamimura N, Taniguchi H, Miyazawa K, Sunamura M, et al. Chromatin immunoprecipitation on microarray analysis of Smad2/3 binding sites reveals roles of ETS1 and TFAP2A in transforming growth factor beta signaling. Mol Cell Biol. 2009;29:172-86 pubmed publisher
    The Smad2 and Smad3 (Smad2/3) proteins are principally involved in the transmission of transforming growth factor beta (TGF-beta) signaling from the plasma membrane to the nucleus...
  41. Gao S, Alarcon C, Sapkota G, Rahman S, Chen P, Goerner N, et al. Ubiquitin ligase Nedd4L targets activated Smad2/3 to limit TGF-beta signaling. Mol Cell. 2009;36:457-68 pubmed publisher
    TGF-beta induces phosphorylation of the transcription factors Smad2 and Smad3 at the C terminus as well as at an interdomain linker region...
  42. Dupont S, Mamidi A, Cordenonsi M, Montagner M, Zacchigna L, Adorno M, et al. FAM/USP9x, a deubiquitinating enzyme essential for TGFbeta signaling, controls Smad4 monoubiquitination. Cell. 2009;136:123-35 pubmed publisher
    ..monoubiquitinated in lysine 519 in vivo, a modification that inhibits Smad4 by impeding association with phospho-Smad2. FAM reverts this negative modification, re-empowering Smad4 function...
  43. Pardali K, Kurisaki A, Moren A, ten Dijke P, Kardassis D, Moustakas A. Role of Smad proteins and transcription factor Sp1 in p21(Waf1/Cip1) regulation by transforming growth factor-beta. J Biol Chem. 2000;275:29244-56 pubmed
    ..We demonstrate that Sp1 physically and directly interacts with Smad2, Smad3, and weakly with Smad4 via their amino-terminal (Mad-Homology 1) domain...
  44. Chen C, Kang Y, Siegel P, Massague J. E2F4/5 and p107 as Smad cofactors linking the TGFbeta receptor to c-myc repression. Cell. 2002;110:19-32 pubmed
    ..Smad proteins therefore mediate transcriptional activation or repression depending on their associated partners. ..
  45. Inman G, Nicolás F, Hill C. Nucleocytoplasmic shuttling of Smads 2, 3, and 4 permits sensing of TGF-beta receptor activity. Mol Cell. 2002;10:283-94 pubmed
    Transforming growth factor (TGF)-beta stimulation leads to phosphorylation and activation of Smad2 and Smad3, which form complexes with Smad4 that accumulate in the nucleus and regulate transcription of target genes...
  46. Kretschmer A, Moepert K, Dames S, Sternberger M, Kaufmann J, Klippel A. Differential regulation of TGF-beta signaling through Smad2, Smad3 and Smad4. Oncogene. 2003;22:6748-63 pubmed
    ..b>Smad2, Smad3 and Smad4 expression were selectively inhibited in differentiation-competent cells by using improved ..
  47. Wilkes M, Murphy S, Garamszegi N, Leof E. Cell-type-specific activation of PAK2 by transforming growth factor beta independent of Smad2 and Smad3. Mol Cell Biol. 2003;23:8878-89 pubmed
    ..PAK2 activation occurs in fibroblast but not epithelial cell cultures and is independent of Smad2 and/or Smad3...
  48. Williams T, Williams M, Heaton J, Gelehrter T, Innis J. Group 13 HOX proteins interact with the MH2 domain of R-Smads and modulate Smad transcriptional activation functions independent of HOX DNA-binding capability. Nucleic Acids Res. 2005;33:4475-84 pubmed
    ..HOXA13 and HOXD13 also bind to other BMP and TGF-beta/Activin-regulated Smad proteins including Smad1 and Smad2, but not Smad4. Furthermore, HOXD13 could be co-immunoprecipitated with Smad1 from cells...
  49. Kuratomi G, Komuro A, Goto K, Shinozaki M, Miyazawa K, Miyazono K, et al. NEDD4-2 (neural precursor cell expressed, developmentally down-regulated 4-2) negatively regulates TGF-beta (transforming growth factor-beta) signalling by inducing ubiquitin-mediated degradation of Smad2 and TGF-beta type I receptor. Biochem J. 2005;386:461-70 pubmed
    ..bound to TGF-beta-specific R-Smads, Smads 2 and 3, in a ligand-dependent manner, and induced degradation of Smad2, but not Smad3...
  50. Hata A, Lagna G, Massague J, Hemmati Brivanlou A. Smad6 inhibits BMP/Smad1 signaling by specifically competing with the Smad4 tumor suppressor. Genes Dev. 1998;12:186-97 pubmed
    ..Smad6 specifically competes with Smad4 for binding to receptor-activated Smad1, yielding an apparently inactive Smad1-Smad6 complex. Therefore, Smad6 selectively antagonizes BMP-activated Smad1 by acting as a Smad4 decoy. ..
  51. Stroschein S, Bonni S, Wrana J, Luo K. Smad3 recruits the anaphase-promoting complex for ubiquitination and degradation of SnoN. Genes Dev. 2001;15:2822-36 pubmed
    ..On TGF-beta stimulation, Smad3 and Smad2 translocate into the nucleus and induce a rapid degradation of SnoN, allowing activation of TGF-beta target genes...
  52. Zhang Y, Feng X, We R, Derynck R. Receptor-associated Mad homologues synergize as effectors of the TGF-beta response. Nature. 1996;383:168-72 pubmed
    ..These results define hMAD-3 and -4 as effectors of the TGF-beta response and demonstrate a function for DPCA-4/hMAD-4 as a tumour suppressor. ..
  53. Lönn P, van der Heide L, Dahl M, Hellman U, Heldin C, Moustakas A. PARP-1 attenuates Smad-mediated transcription. Mol Cell. 2010;40:521-32 pubmed publisher
    ..Activation of TGF-? receptors leads to phosphorylation of Smad2 and Smad3, which oligomerize with Smad4 and accumulate in the nucleus where they recognize gene regulatory regions ..
  54. Matsuura I, Lai C, Chiang K. Functional interaction between Smad3 and S100A4 (metastatin-1) for TGF-beta-mediated cancer cell invasiveness. Biochem J. 2010;426:327-35 pubmed publisher
    ..S100A4 can potentiate transcriptional activity of Smad3 and the related Smad2. When exogenously expressed in MCF10CA1a...
  55. Macias Silva M, Abdollah S, Hoodless P, Pirone R, Attisano L, Wrana J. MADR2 is a substrate of the TGFbeta receptor and its phosphorylation is required for nuclear accumulation and signaling. Cell. 1996;87:1215-24 pubmed
    ..Here, we demonstrate that MADR2 and not the related protein DPC4 transiently interacts with the TGFbeta receptor and is directly phosphorylated by ..
  56. Oft M, Akhurst R, Balmain A. Metastasis is driven by sequential elevation of H-ras and Smad2 levels. Nat Cell Biol. 2002;4:487-94 pubmed
    ..Here we show that during multistage tumorigenesis, discrete expression thresholds of activated Smad2 and H-ras are sequentially surpassed, driving tumour progression through distinct phases from a differentiated ..
  57. Pan D, Estévez Salmerón L, Stroschein S, Zhu X, He J, Zhou S, et al. The integral inner nuclear membrane protein MAN1 physically interacts with the R-Smad proteins to repress signaling by the transforming growth factor-{beta} superfamily of cytokines. J Biol Chem. 2005;280:15992-6001 pubmed
    ..Thus, MAN1 represents a new class of R-Smad regulators and defines a previously unrecognized regulatory step at the nuclear periphery. ..
  58. Stroschein S, Wang W, Zhou S, Zhou Q, Luo K. Negative feedback regulation of TGF-beta signaling by the SnoN oncoprotein. Science. 1999;286:771-4 pubmed
    ..The SnoN oncoprotein was found to interact with Smad2 and Smad4 and to repress their abilities to activate transcription through recruitment of the transcriptional ..
  59. Bruna A, Darken R, Rojo F, Ocana A, Peñuelas S, Arias A, et al. High TGFbeta-Smad activity confers poor prognosis in glioma patients and promotes cell proliferation depending on the methylation of the PDGF-B gene. Cancer Cell. 2007;11:147-60 pubmed
    ..The epigenetic regulation of the PDGF-B gene dictates whether TGFbeta acts as an oncogenic factor inducing PDGF-B and proliferation in human glioma. ..
  60. Thuault S, Tan E, Peinado H, Cano A, Heldin C, Moustakas A. HMGA2 and Smads co-regulate SNAIL1 expression during induction of epithelial-to-mesenchymal transition. J Biol Chem. 2008;283:33437-46 pubmed publisher
    ..The data propose that HMGA2 acts in a gene-specific manner to orchestrate the transcriptional network necessary for the EMT program. ..
  61. Hoot K, Lighthall J, Han G, Lu S, Li A, Ju W, et al. Keratinocyte-specific Smad2 ablation results in increased epithelial-mesenchymal transition during skin cancer formation and progression. J Clin Invest. 2008;118:2722-32 pubmed publisher
    TGF-beta and its signaling mediators, Smad2, -3, and -4, are involved with tumor suppression and promotion functions...
  62. Liu F, Massague J, Ruiz i Altaba A. Carboxy-terminally truncated Gli3 proteins associate with Smads. Nat Genet. 1998;20:325-6 pubmed
  63. Suzuki H, Yagi K, Kondo M, Kato M, Miyazono K, Miyazawa K. c-Ski inhibits the TGF-beta signaling pathway through stabilization of inactive Smad complexes on Smad-binding elements. Oncogene. 2004;23:5068-76 pubmed
    ..DNA-affinity precipitation analysis revealed that c-Ski enhances the binding of Smad2 and 4, and to a lesser extent Smad3, to both CAGA and TGF-beta1 inhibitory element probes...
  64. Besser D. Expression of nodal, lefty-a, and lefty-B in undifferentiated human embryonic stem cells requires activation of Smad2/3. J Biol Chem. 2004;279:45076-84 pubmed
    ..High expression of these genes in undifferentiated cells is maintained by activation of the transcription factor Smad2/3, downstream of the activin-linked kinases (ALK) 4/5/7...