SMAD9

Summary

Gene Symbol: SMAD9
Description: SMAD family member 9
Alias: MADH6, MADH9, PPH2, SMAD8, SMAD8/9, SMAD8A, SMAD8B, mothers against decapentaplegic homolog 9, MAD homolog 9, Mothers against decapentaplegic, drosophila, homolog of, 9, SMAD, mothers against DPP homolog 9
Species: human
Products:     SMAD9

Top Publications

  1. Miyazono K. TGF-beta signaling by Smad proteins. Cytokine Growth Factor Rev. 2000;11:15-22 pubmed
    ..Through interaction with different transcription factors and transcriptional co-activators or co-repressors, Smads may exhibit specific effects in various cell types. ..
  2. El Safadi M, Shinwari T, Al Malki S, Manikandan M, Mahmood A, Aldahmash A, et al. Convergence of TGFβ and BMP signaling in regulating human bone marrow stromal cell differentiation. Sci Rep. 2019;9:4977 pubmed publisher
    ..revealed significant downregulation of several TGFβ responsive genes, namely, TAGLN, TMP1, ACTA2, TGFβ2, SMAD6, SMAD9, BMP2, and BMP4 in hBMSC-Bone cells and upregulation on SERPINB2 and NOG...
  3. Chen Y, Ye C, Chen J, Lin D, Wang H, Wang S. Association of the gene polymorphisms of BMPR2, ACVRL1, SMAD9 and their interactions with the risk of essential hypertension in the Chinese Han population. Biosci Rep. 2019;39: pubmed publisher
    ..activin receptor-like kinase 1 (ACVRL1) gene, and the rs397514716 and rs121918359 loci of the mothers against decapentaplegic homolog 9 (SMAD9) gene with the risk of EH in the Chinese Han population...
  4. Yu D, Zhang L, Wang H, Chen F, Chen J, Zhang Z, et al. A potential role for SMAD9 in goose follicular selection through regulation of mRNA levels of luteinizing hormone receptor. Theriogenology. 2018;: pubmed publisher
    ..Nonetheless, the mechanism underlying the priority of selecting of hierarchical follicles is completely unknown. SMAD9 is one of the important transcription factors in the BMP/SMAD pathway and is involved in goose follicular ..
  5. Tsukamoto S, Mizuta T, Fujimoto M, Ohte S, Osawa K, Miyamoto A, et al. Smad9 is a new type of transcriptional regulator in bone morphogenetic protein signaling. Sci Rep. 2014;4:7596 pubmed publisher
    Smad1, Smad5 and Smad9 (also known as Smad8) are activated by phosphorylation by bone morphogenetic protein (BMP)-bound type I receptor kinases...
  6. Alkema M, Goumans M, Kruithof B. Immunofluorescent Visualization of BMP Signaling Activation on Paraffin-Embedded Tissue Sections. Methods Mol Biol. 2019;1891:191-200 pubmed publisher
    ..Phosphorylated Smad1, Smad5, and Smad9 are the activated signaling molecules of the BMP pathway that transfer BMP signals from the cell surface to the ..
  7. Drake K, Dunmore B, McNelly L, Morrell N, Aldred M. Correction of nonsense BMPR2 and SMAD9 mutations by ataluren in pulmonary arterial hypertension. Am J Respir Cell Mol Biol. 2013;49:403-9 pubmed publisher
    ..vascular disease caused by heterozygous mutations in the bone morphogenetic protein (BMP) pathway genes, BMPR2 and SMAD9. One noncanonical function of BMP signaling regulates biogenesis of a subset of microRNAs...
  8. Schulten H, Al Mansouri Z, Baghallab I, Bagatian N, Subhi O, Karim S, et al. Comparison of microarray expression profiles between follicular variant of papillary thyroid carcinomas and follicular adenomas of the thyroid. BMC Genomics. 2015;16 Suppl 1:S7 pubmed publisher
    ..expressed molecules including vitamin D (1,25- dihydroxyvitamin D3) receptor (VDR), SMAD family member 9 (SMAD9), v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT), and RXRG...
  9. Xu J, Li J, Wang H, Wang G, Chen J, Huang P, et al. A novel SMAD family protein, SMAD9 is involved in follicular initiation and changes egg yield of geese via synonymous mutations in exon1 and intron2. Mol Biol Rep. 2015;42:289-302 pubmed publisher
    ..For the first time, a novel SMAD family protein SMAD9 (EST CJ111007) was found to be involved in follicular initiation and used to be a candidate gene...

More Information

Publications47

  1. Kokaji E, Shimomura A, Minamisaka T, Nakajima T, Miwa S, Hatta H, et al. Endoglin (CD105) and SMAD4 regulate spheroid formation and the suppression of the invasive ability of human pancreatic cancer cells. Int J Oncol. 2018;52:892-900 pubmed publisher
    ..In the cells in which ENG was knocked down, the decreased mRNA expression of TGF-? receptor type 2 (TGFBR2) and SMAD9 was observed, as well as a change in the expression of pSMAD1/5/9, and a tendency of spheroids to decrease in size...
  2. Sun Y, Lin X, Li L. Identification of Biomarkers for Schistosoma-Associated Pulmonary Arterial Hypertension Based on RNA-Seq Data of Mouse Whole Lung Tissues. Lung. 2017;195:377-385 pubmed publisher
    ..Downregulated DEGs (i.e., Smad9 (SMAD family member 9), BMPR2 (bone morphogenetic protein type 2 receptor), and Eng (endoglin)) were ..
  3. Xi Q, Liu Z, Zhao Z, Luo Q, Huang Z. High Frequency of Pulmonary Hypertension-Causing Gene Mutation in Chinese Patients with Chronic Thromboembolic Pulmonary Hypertension. PLoS ONE. 2016;11:e0147396 pubmed publisher
    ..In this study, we analyzed 7 PAH-causing genes including BMPR2, ACVRL1, ENG, SMAD9, CAV1, KCNK3, and CBLN2 in 49 CTEPH patients and 17 patients recovered from pulmonary embolism (PE) but without ..
  4. Guo C, Liu S, Dong P, Zhao D, Wang C, Tao Z, et al. Akbu-LAAO exhibits potent anti-tumor activity to HepG2 cells partially through produced H2O2 via TGF-β signal pathway. Sci Rep. 2015;5:18215 pubmed publisher
    ..TGF-β pathway related molecules CYR61, p53, GDF15, TOB1, BTG2, BMP2, BMP6, SMAD9, JUN, JUNB, LOX, CCND1, CDK6, GADD45A, CDKN1A were deregulated in HepG2 following Akbu-LAAO stimulation...
  5. Lee J, Lee G, Kwon S, Jeong J, Ha Y, Kim W, et al. CREBZF, a novel Smad8-binding protein. Mol Cell Biochem. 2012;368:147-53 pubmed publisher
    ..regulation of BMP mediating Smads, we performed yeast two-hybrid screening using the Mad homology 2(MH2) domain of Smad8 as bait...
  6. Dexheimer V, Gabler J, Bomans K, Sims T, Omlor G, Richter W. Differential expression of TGF-β superfamily members and role of Smad1/5/9-signalling in chondral versus endochondral chondrocyte differentiation. Sci Rep. 2016;6:36655 pubmed publisher
  7. Ngeow J, Yu W, Yehia L, Niazi F, Chen J, Tang X, et al. Exome Sequencing Reveals Germline SMAD9 Mutation That Reduces Phosphatase and Tensin Homolog Expression and Is Associated With Hamartomatous Polyposis and Gastrointestinal Ganglioneuromas. Gastroenterology. 2015;149:886-9.e5 pubmed publisher
    ..Exome sequencing identified a germline heterozygous mutation in SMAD9 (SMAD9(V90M)). This mutation was predicted to be an activating mutation...
  8. Lee N, Ray B, How T, Blobe G. Endoglin promotes transforming growth factor beta-mediated Smad 1/5/8 signaling and inhibits endothelial cell migration through its association with GIPC. J Biol Chem. 2008;283:32527-33 pubmed publisher
    ..These studies define a novel mechanism for the regulation of endoglin signaling and function in endothelial cells and demonstrate a new role for GIPC in TGF-beta signaling. ..
  9. Topper J, Cai J, Qiu Y, Anderson K, Xu Y, Deeds J, et al. Vascular MADs: two novel MAD-related genes selectively inducible by flow in human vascular endothelium. Proc Natl Acad Sci U S A. 1997;94:9314-9 pubmed
  10. García Rivas G, Jerjes Sánchez C, Rodriguez D, Garcia Pelaez J, Trevino V. A systematic review of genetic mutations in pulmonary arterial hypertension. BMC Med Genet. 2017;18:82 pubmed publisher
    ..the bone morphogenic proteins and transforming Growth Factor-? pathways, such as the BMPR2, ACVRL1, CAV1, ENG, and SMAD9. To provide an expanded view of the genes and variants associated with PAH, we performed a systematic literature ..
  11. Wrana J, Attisano L. The Smad pathway. Cytokine Growth Factor Rev. 2000;11:5-13 pubmed
    ..In addition, we will summarize recent findings on the role of Smads as transcriptional co-modulators. ..
  12. Katakawa Y, Funaba M, Murakami M. Smad8/9 Is Regulated Through the BMP Pathway. J Cell Biochem. 2016;117:1788-96 pubmed publisher
    ..BMP4 potentiated the up-regulation of Smad8/9 expression in C2C12, H9c2, 3T3-L1, HepG2, B16, and primary fibroblasts...
  13. Yan X, Liao H, Cheng M, Shi X, Lin X, Feng X, et al. Smad7 Protein Interacts with Receptor-regulated Smads (R-Smads) to Inhibit Transforming Growth Factor-β (TGF-β)/Smad Signaling. J Biol Chem. 2016;291:382-92 pubmed publisher
    ..These results shed new light on the regulation of TGF-β signaling by Smad7. ..
  14. Nohe A, Keating E, Knaus P, Petersen N. Signal transduction of bone morphogenetic protein receptors. Cell Signal. 2004;16:291-9 pubmed
    ..This article reviews the current state of BMP receptor signaling and provides a summary of the crosstalk of the BMP receptor pathway with other major signaling pathways. ..
  15. Kahata K, Hayashi M, Asaka M, Hellman U, Kitagawa H, Yanagisawa J, et al. Regulation of transforming growth factor-beta and bone morphogenetic protein signalling by transcriptional coactivator GCN5. Genes Cells. 2004;9:143-51 pubmed
    ..In conclusion we identified GCN5 as a Smad-binding transcriptional coactivator which positively regulates both TGF-beta and BMP signalling pathways. ..
  16. Park S, Lee Y, Lee H, Seki T, Hong K, Park J, et al. B-cell translocation gene 2 (Btg2) regulates vertebral patterning by modulating bone morphogenetic protein/smad signaling. Mol Cell Biol. 2004;24:10256-62 pubmed
    ..In view of the genetic evidence that reduced BMP signaling causes posteriorization of the vertebral pattern, we propose that the observed vertebral phenotype in Btg2-null mice is due to attenuated BMP signaling. ..
  17. Dalvi P, O Brien Ladner A, Dhillon N. Downregulation of bone morphogenetic protein receptor axis during HIV-1 and cocaine-mediated pulmonary smooth muscle hyperplasia: implications for HIV-related pulmonary arterial hypertension. Arterioscler Thromb Vasc Biol. 2013;33:2585-95 pubmed publisher
    ..Simultaneous exposure of pulmonary smooth muscle cells to viral protein(s) and cocaine exacerbates downregulation of BMPR axis that may result in enhanced pulmonary vasculature aberrations in HIV+IVDUs...
  18. Nicklas D, Saiz L. Computational modelling of Smad-mediated negative feedback and crosstalk in the TGF-? superfamily network. J R Soc Interface. 2013;10:20130363 pubmed publisher
  19. Watanabe T, Suzuki M, Omori Y, Hishigaki H, Horie M, Kanemoto N, et al. Cloning and characterization of a novel member of the human Mad gene family (MADH6). Genomics. 1997;42:446-51 pubmed
    ..This gene, which we designated MADH6, resides on 13q12-q14 between BRCA2 and RB, a region that frequently displays loss of heterozygosity in breast, ..
  20. Wahdan Alaswad R, Bane K, Song K, Shola D, Garcia J, Danielpour D. Inhibition of mTORC1 kinase activates Smads 1 and 5 but not Smad8 in human prostate cancer cells, mediating cytostatic response to rapamycin. Mol Cancer Res. 2012;10:821-33 pubmed publisher
    ..hairpin RNA-based gene silencing and gene overexpression approaches reveal that Smads 1 and 5 mediate, whereas Smad8 represses, rapamycin-induced cell death and expression of the bone morphogenetic protein (BMP) transcriptional ..
  21. Hoover L, Kubalak S. Holding their own: the noncanonical roles of Smad proteins. Sci Signal. 2008;1:pe48 pubmed publisher
    ..Investigating these interactions will likely yield more evidence that Smads serve important and diverse purposes beyond their original reported function as signal transducers in the TGF-beta pathway. ..
  22. Shintani M, Yagi H, Nakayama T, Saji T, Matsuoka R. A new nonsense mutation of SMAD8 associated with pulmonary arterial hypertension. J Med Genet. 2009;46:331-7 pubmed publisher
    ..We screened for mutations in ENDOGLIN(ENG), SMAD1, SMAD2, SMAD3, SMAD4, SMAD5, SMAD6 and SMAD8 genes, which are involved in the TGF-beta/BMP signallings, in 23 patients with IPAH who had no mutations in BMPR2 ..
  23. Wang W, Mariani F, Harland R, Luo K. Ski represses bone morphogenic protein signaling in Xenopus and mammalian cells. Proc Natl Acad Sci U S A. 2000;97:14394-9 pubmed
    ..Upon stimulation with BMP, Smad1, Smad5, and Smad8 are phosphorylated by the activated BMP receptors, form a complex with Smad4, and translocate into the nucleus, ..
  24. Monzen K, Ito Y, Naito A, Kasai H, Hiroi Y, Hayashi D, et al. A crucial role of a high mobility group protein HMGA2 in cardiogenesis. Nat Cell Biol. 2008;10:567-74 pubmed publisher
    ..5 gene, both in P19CL6 cells and in transgenic Xenopus embryos. Thus, HMGA2 is a positive regulator of Nkx2.5 gene expression and is essential for normal cardiac development. ..
  25. 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. ..
  26. 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. ..
  27. Nishita M, Ueno N, Shibuya H. Smad8B, a Smad8 splice variant lacking the SSXS site that inhibits Smad8-mediated signalling. Genes Cells. 1999;4:583-91 pubmed
    ..Smad8 is a downstream signalling mediator of ALK2/ActRIA. We have cloned a splice variant of Smad8, designated Smad8B. The Smad8 and Smad8B cDNAs are identical in sequence, except that Smad8B lacks a portion encoding 47 amino acids, ..
  28. Verschueren K, Huylebroeck D. Remarkable versatility of Smad proteins in the nucleus of transforming growth factor-beta activated cells. Cytokine Growth Factor Rev. 1999;10:187-99 pubmed
    ..We summarize some of the most recent data with regard to this aspect in this rapidly advancing field. ..
  29. Huertas A, Tu L, Guignabert C. New targets for pulmonary arterial hypertension: going beyond the currently targeted three pathways. Curr Opin Pulm Med. 2017;23:377-385 pubmed publisher
    ..In this review, we highlight some recent biological findings and discuss the opportunities that could lead to the identification of new promising targets in PAH paving the way for future therapeutic strategies. ..
  30. Liu Y, Ren W, Warburton R, Toksoz D, Fanburg B. Serotonin induces Rho/ROCK-dependent activation of Smads 1/5/8 in pulmonary artery smooth muscle cells. FASEB J. 2009;23:2299-306 pubmed publisher
    ..Rho and Rho kinase also participate in the activation of Smads by BMP. ..
  31. Shi W, Chang C, Nie S, Xie S, Wan M, Cao X. Endofin acts as a Smad anchor for receptor activation in BMP signaling. J Cell Sci. 2007;120:1216-24 pubmed
    ..Taken together, our results suggest that endofin plays an important role in both positive and negative feedback regulation of the BMP signaling pathway. ..
  32. Su D, Zhu S, Han X, Feng Y, Huang H, Ren G, et al. BMP4-Smad signaling pathway mediates adriamycin-induced premature senescence in lung cancer cells. J Biol Chem. 2009;284:12153-64 pubmed publisher
    ..The present study provides useful clues to the evaluation of the potentiality of BMP4 as a responsive molecular target for cancer chemotherapy. ..
  33. Yoshida Y, Tanaka S, Umemori H, Minowa O, Usui M, Ikematsu N, et al. Negative regulation of BMP/Smad signaling by Tob in osteoblasts. Cell. 2000;103:1085-97 pubmed
    ..The results indicate that Tob negatively regulates osteoblast proliferation and differentiation by suppressing the activity of the receptor-regulated Smad proteins. ..
  34. Chen F, Lin X, Xu P, Zhang Z, Chen Y, Wang C, et al. Nuclear Export of Smads by RanBP3L Regulates Bone Morphogenetic Protein Signaling and Mesenchymal Stem Cell Differentiation. Mol Cell Biol. 2015;35:1700-11 pubmed publisher
    ..is stringently controlled through reversible phosphorylation and nucleocytoplasmic shuttling of Smad1, Smad5, and Smad8 (Smad1/5/8). However, how the nuclear export of Smad1/5/8 is regulated remains unclear...
  35. Tang Y, Xie H, Chen J, Geng L, Chen H, Li X, et al. Activated NF-?B in bone marrow mesenchymal stem cells from systemic lupus erythematosus patients inhibits osteogenic differentiation through downregulating Smad signaling. Stem Cells Dev. 2013;22:668-78 pubmed publisher
  36. Chen D, Zhao M, Mundy G. Bone morphogenetic proteins. Growth Factors. 2004;22:233-41 pubmed
    ..et al. (1997) "Smad8 mediates the signaling of the receptor serine kinase", Proc. Natl Acad. Sci. USA 94, 12938-12943; Nishimura R...
  37. Nishida T, Kubota S, Aoyama E, Takigawa M. Impaired glycolytic metabolism causes chondrocyte hypertrophy-like changes via promotion of phospho-Smad1/5/8 translocation into nucleus. Osteoarthritis Cartilage. 2013;21:700-9 pubmed publisher
    ..These findings suggest that decreased ATP production by NaF promotes hypertrophy-like changes via activation of phospho-Smad1/5/8 in the presence of lactate. Novel metabolic aspects of OA pathogenesis are indicated herein. ..