Gene Symbol: SMURF1
Description: SMAD specific E3 ubiquitin protein ligase 1
Alias: E3 ubiquitin-protein ligase SMURF1, E3 ubiquitin ligase SMURF1, HECT-type E3 ubiquitin transferase SMURF1, Smad ubiquitination regulatory factor 1, Smad-specific E3 ubiquitin ligase 1, hSMURF1
Species: human
Products:     SMURF1

Top Publications

  1. Asanuma K, Yanagida Asanuma E, Faul C, Tomino Y, Kim K, Mundel P. Synaptopodin orchestrates actin organization and cell motility via regulation of RhoA signalling. Nat Cell Biol. 2006;8:485-91 pubmed
    ..We show that synaptopodin induces stress fibres by competitive blocking of Smurf1-mediated ubiquitination of RhoA, thereby preventing the targeting of RhoA for proteasomal degradation...
  2. Fukunaga E, Inoue Y, Komiya S, Horiguchi K, Goto K, Saitoh M, et al. Smurf2 induces ubiquitin-dependent degradation of Smurf1 to prevent migration of breast cancer cells. J Biol Chem. 2008;283:35660-7 pubmed publisher
    ..Smad ubiquitin regulatory factor 1 (Smurf1) and Smurf2 are E3 ubiquitin ligases, which suppress transforming growth factor-beta (TGF-beta) family signaling ..
  3. Cao Y, Wang C, Zhang X, Xing G, Lu K, Gu Y, et al. Selective small molecule compounds increase BMP-2 responsiveness by inhibiting Smurf1-mediated Smad1/5 degradation. Sci Rep. 2014;4:4965 pubmed publisher
    The ubiquitin ligase Smad ubiquitination regulatory factor-1 (Smurf1) negatively regulates bone morphogenetic protein (BMP) pathway by ubiquitinating certain signal components for degradation...
  4. Nie J, Liu L, Wu M, Xing G, He S, Yin Y, et al. HECT ubiquitin ligase Smurf1 targets the tumor suppressor ING2 for ubiquitination and degradation. FEBS Lett. 2010;584:3005-12 pubmed publisher
    ..Here we show that the homologous to E6AP carboxyl terminus (HECT)-type ubiquitin ligase Smad ubiquitination regulatory factor 1 (Smurf1) interacts with and targets ING2 for poly-ubiquitination and proteasomal degradation...
  5. Ozdamar B, Bose R, Barrios Rodiles M, Wang H, Zhang Y, Wrana J. Regulation of the polarity protein Par6 by TGFbeta receptors controls epithelial cell plasticity. Science. 2005;307:1603-9 pubmed
    ..TGFbeta-dependent EMT in mammary gland epithelial cells and controls the interaction of Par6 with the E3 ubiquitin ligase Smurf1. Smurf1, in turn, targets the guanosine triphosphatase RhoA for degradation, thereby leading to a loss ..
  6. Wan L, Zou W, Gao D, Inuzuka H, Fukushima H, Berg A, et al. Cdh1 regulates osteoblast function through an APC/C-independent modulation of Smurf1. Mol Cell. 2011;44:721-33 pubmed publisher
    ..Here, we report that Cdh1, but not Cdc20, promotes the E3 ligase activity of Smurf1. This is mediated by disruption of an autoinhibitory Smurf1 homodimer and is independent of APC/Cdh1 E3 ligase ..
  7. 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
    ..Nedd4L is not interchangeable with Smurf1, a ubiquitin ligase that targets BMP-activated, linker-phosphorylated Smad1...
  8. Lu K, Yin X, Weng T, Xi S, Li L, Xing G, et al. Targeting WW domains linker of HECT-type ubiquitin ligase Smurf1 for activation by CKIP-1. Nat Cell Biol. 2008;10:994-1002 pubmed publisher
    ..Smad ubiquitylation regulatory factor 1 (Smurf1), a C2-WW-HECT-domain E3, is crucial for bone homeostasis, in which it suppresses osteoblast activity...
  9. Chan M, Nguyen P, Davis B, Ohoka N, Hayashi H, Du K, et al. A novel regulatory mechanism of the bone morphogenetic protein (BMP) signaling pathway involving the carboxyl-terminal tail domain of BMP type II receptor. Mol Cell Biol. 2007;27:5776-89 pubmed
    ..BMP stimulation, Trb3 dissociates from BMPRII-TD and triggers degradation of Smad ubiquitin regulatory factor 1 (Smurf1), which results in the stabilization of BMP receptor-regulated Smads and potentiation of the Smad pathway...

More Information


  1. Xie P, Zhang M, He S, Lu K, Chen Y, Xing G, et al. The covalent modifier Nedd8 is critical for the activation of Smurf1 ubiquitin ligase in tumorigenesis. Nat Commun. 2014;5:3733 pubmed publisher
    ..Here we show that the C2-WW-HECT ligase Smurf1 is activated by neddylation...
  2. Wang H, Ogunjimi A, Zhang Y, Ozdamar B, Bose R, Wrana J. Degradation of RhoA by Smurf1 ubiquitin ligase. Methods Enzymol. 2006;406:437-47 pubmed
    ..We found that Smurf1, a HECT domain E3 ubiquitin ligase, could specifically target RhoA but not Cdc42 or Rac1 for degradation...
  3. Sangadala S, Boden S, Metpally R, Reddy B. Modeling and analysis of molecularinteraction between Smurf1-WW2 domain and various isoforms of LIM mineralization protein. Proteins. 2007;68:690-701 pubmed
    ..the mode of action of LMP-1 led to the determination that LMP-1 interacts with Smad Ubiquitin Regulatory Factor-1 (Smurf1). Smurf1 targets osteogenic Smads, Smad1/5, for ubiquitin-mediated proteasomal degradation...
  4. Koinuma D, Shinozaki M, Komuro A, Goto K, Saitoh M, Hanyu A, et al. Arkadia amplifies TGF-beta superfamily signalling through degradation of Smad7. EMBO J. 2003;22:6458-70 pubmed
    ..In contrast to Smurf1, which interacts with TGF-beta receptor complexes through Smad7 and degrades them, Arkadia fails to associate with ..
  5. Sheng Y, Hong J, Doherty R, Srikumar T, Shloush J, Avvakumov G, et al. A human ubiquitin conjugating enzyme (E2)-HECT E3 ligase structure-function screen. Mol Cell Proteomics. 2012;11:329-41 pubmed publisher
    ..Our data set represents the first comprehensive analysis of E2-HECT E3 interactions, and thus provides a framework for better understanding the molecular mechanisms of ubiquitylation. ..
  6. Yamashita M, Ying S, Zhang G, Li C, Cheng S, Deng C, et al. Ubiquitin ligase Smurf1 controls osteoblast activity and bone homeostasis by targeting MEKK2 for degradation. Cell. 2005;121:101-13 pubmed
    ..Here we show that Smurf1, a HECT domain ubiquitin ligase, has a specific physiological role in suppressing the osteogenic activity of ..
  7. Guo X, Shen S, Song S, He S, Cui Y, Xing G, et al. The E3 ligase Smurf1 regulates Wolfram syndrome protein stability at the endoplasmic reticulum. J Biol Chem. 2011;286:18037-47 pubmed publisher
    The HECT-type ubiquitin ligase (E3) Smad ubiquitination regulatory factor 1 (Smurf1) targets various substrates, including Smad1/5, RhoA, Prickle 1, MEKK2, and JunB for degradation and thereby regulates adult bone formation and embryonic ..
  8. Morén A, Imamura T, Miyazono K, Heldin C, Moustakas A. Degradation of the tumor suppressor Smad4 by WW and HECT domain ubiquitin ligases. J Biol Chem. 2005;280:22115-23 pubmed
    ..Smad4 co-localized with Smad7 and Smurf1 primarily in the cytoplasm and in peripheral cell protrusions...
  9. Shen R, Chen M, Wang Y, Kaneki H, Xing L, O Keefe R, et al. Smad6 interacts with Runx2 and mediates Smad ubiquitin regulatory factor 1-induced Runx2 degradation. J Biol Chem. 2006;281:3569-76 pubmed
    ..In previous studies we discovered that E3 ubiquitin ligase Smad ubiquitin regulatory factor 1 (Smurf1) induces Runx2 degradation in a ubiquitin-proteasome-dependent manner, and Smurf1 plays an important role in ..
  10. Kwei K, Shain A, Bair R, Montgomery K, Karikari C, van de Rijn M, et al. SMURF1 amplification promotes invasiveness in pancreatic cancer. PLoS ONE. 2011;6:e23924 pubmed publisher immunodeficient mice to enrich the cancer epithelial fraction), we define a 325 Kb minimal amplicon spanning SMURF1, an E3 ubiquitin ligase and known negative regulator of transforming growth factor β (TGFβ) growth inhibitory ..
  11. Suzuki C, Murakami G, Fukuchi M, Shimanuki T, Shikauchi Y, Imamura T, et al. Smurf1 regulates the inhibitory activity of Smad7 by targeting Smad7 to the plasma membrane. J Biol Chem. 2002;277:39919-25 pubmed
    Smad ubiquitin regulatory factor 1 (Smurf1), a HECT-type E3 ubiquitin ligase, interacts with inhibitory Smad7 and induces cytoplasmic localization of Smad7...
  12. Sapkota G, Alarcon C, Spagnoli F, Brivanlou A, Massague J. Balancing BMP signaling through integrated inputs into the Smad1 linker. Mol Cell. 2007;25:441-54 pubmed
    ..linker phosphorylation restricts Smad1 activity by enabling Smad1 recognition by the HECT-domain ubiquitin ligase Smurf1. Besides causing Smad1 polyubiquitination, Smurf1 binding inhibits the interaction of Smad1 with the nuclear ..
  13. Narimatsu M, Bose R, Pye M, Zhang L, Miller B, Ching P, et al. Regulation of planar cell polarity by Smurf ubiquitin ligases. Cell. 2009;137:295-307 pubmed publisher
    ..Here, we report an unexpected role for Smurfs in controlling PCP and CE. Mice mutant for Smurf1 and Smurf2 display PCP defects in the cochlea and CE defects that include a failure to close the neural tube...
  14. Wang H, Zhang Y, Ozdamar B, Ogunjimi A, Alexandrova E, Thomsen G, et al. Regulation of cell polarity and protrusion formation by targeting RhoA for degradation. Science. 2003;302:1775-9 pubmed
    ..We found that Smurf1, a HECT domain E3 ubiquitin ligase, regulated cell polarity and protrusive activity and was required to maintain ..
  15. 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
    ..Importantly, WWP1 and Smurfs were expressed in distinct patterns in human tissues and carcinoma cell lines, suggesting unique pathophysiological roles of WWP1 and Smurfs. ..
  16. Huang C, Rajfur Z, Yousefi N, Chen Z, Jacobson K, Ginsberg M. Talin phosphorylation by Cdk5 regulates Smurf1-mediated talin head ubiquitylation and cell migration. Nat Cell Biol. 2009;11:624-30 pubmed publisher
    ..Here we show that talin head binds Smurf1, an E3 ubiquitin ligase involved in cell polarity and migration, more tightly than full-length talin does and that ..
  17. Chen D, Zhao M, Mundy G. Bone morphogenetic proteins. Growth Factors. 2004;22:233-41 pubmed
    ..A significant advancement about the understanding of in vivo functions of BMP ligands, receptors and signaling molecules has been achieved in recent years. ..
  18. Nie J, Xie P, Liu L, Xing G, Chang Z, Yin Y, et al. Smad ubiquitylation regulatory factor 1/2 (Smurf1/2) promotes p53 degradation by stabilizing the E3 ligase MDM2. J Biol Chem. 2010;285:22818-30 pubmed publisher
    ..Here, we show that the HECT-type E3 ligase Smurf1/2 (Smad ubiquitylation regulatory factor 1/2) promotes p53 degradation by enhancing the activity of the E3 ligase ..
  19. Sahai E, Garcia Medina R, Pouyssegur J, Vial E. Smurf1 regulates tumor cell plasticity and motility through degradation of RhoA leading to localized inhibition of contractility. J Cell Biol. 2007;176:35-42 pubmed
    ..It has been reported that RhoA is targeted for degradation at the leading edge of migrating cells by the E3 ubiquitin ligase Smurf1, and that this is required for the formation of protrusions...
  20. Murakami G, Watabe T, Takaoka K, Miyazono K, Imamura T. Cooperative inhibition of bone morphogenetic protein signaling by Smurf1 and inhibitory Smads. Mol Biol Cell. 2003;14:2809-17 pubmed
    ..In addition, Smurf1 associates with transforming growth factor-beta type I receptor through the inhibitory Smad (I-Smad) Smad7 and ..
  21. Suzuki A, Shibata T, Shimada Y, Murakami Y, Horii A, Shiratori K, et al. Identification of SMURF1 as a possible target for 7q21.3-22.1 amplification detected in a pancreatic cancer cell line by in-house array-based comparative genomic hybridization. Cancer Sci. 2008;99:986-94 pubmed publisher
    ..lines, as well as immunohistochemical analyses of candidates in primary tumors of PC, we successfully identified SMURF1 as having the greatest potential as a 7q21.3-22.1 amplification target...
  22. Cheng P, Lu H, Shelly M, Gao H, Poo M. Phosphorylation of E3 ligase Smurf1 switches its substrate preference in support of axon development. Neuron. 2011;69:231-43 pubmed publisher
    ..Here we report that protein kinase A (PKA)-dependent phosphorylation of Smad Ubiquitin Regulatory Factor 1 (Smurf1) can switch its substrate preference between two proteins of opposing actions on axon development...
  23. Liu Y, Liu W, Hu C, Xue Z, Wang G, Ding B, et al. MiR-17 modulates osteogenic differentiation through a coherent feed-forward loop in mesenchymal stem cells isolated from periodontal ligaments of patients with periodontitis. Stem Cells. 2011;29:1804-16 pubmed publisher
    ..Furthermore, inflammation in the microenvironment promoted the expression of Smad ubiquitin regulatory factor one (Smurf1), an important negative regulator of MSC osteogenic differentiation...
  24. Ebisawa T, Fukuchi M, Murakami G, Chiba T, Tanaka K, Imamura T, et al. Smurf1 interacts with transforming growth factor-beta type I receptor through Smad7 and induces receptor degradation. J Biol Chem. 2001;276:12477-80 pubmed
    ..Here we show that Smurf1, an E3 ubiquitin ligase for bone morphogenetic protein-specific Smads, also interacts with Smad7 and induces Smad7 ..
  25. Kannan M, Lee S, Schwedhelm Domeyer N, Stegmuller J. The E3 ligase Cdh1-anaphase promoting complex operates upstream of the E3 ligase Smurf1 in the control of axon growth. Development. 2012;139:3600-12 pubmed publisher
    ..In this study, we identify in rodents the E3 ligase Smurf1 as a novel substrate of Cdh1-APC and that Cdh1 targets Smurf1 for degradation in a destruction box-dependent ..
  26. Zhu H, Kavsak P, Abdollah S, Wrana J, Thomsen G. A SMAD ubiquitin ligase targets the BMP pathway and affects embryonic pattern formation. Nature. 1999;400:687-93 pubmed
    ..Here we describe Smurf1, a new member of the Hect family of E3 ubiquitin ligases...
  27. Lu K, Li P, Zhang M, Xing G, Li X, Zhou W, et al. Pivotal role of the C2 domain of the Smurf1 ubiquitin ligase in substrate selection. J Biol Chem. 2011;286:16861-70 pubmed publisher
    The C2-WW-HECT-type ubiquitin ligases Smurf1 and Smurf2 play a critical role in embryogenesis and adult bone homeostasis via regulation of bone morphogenetic protein, Wnt, and RhoA signaling pathways...
  28. Aragón E, Goerner N, Zaromytidou A, Xi Q, Escobedo A, Massagué J, et al. A Smad action turnover switch operated by WW domain readers of a phosphoserine code. Genes Dev. 2011;25:1275-88 pubmed publisher
    ..phosphorylations that mediate the binding of YAP and Pin1 for transcriptional action, and of ubiquitin ligases Smurf1 and Nedd4L for Smad destruction...
  29. Chang H, Zhang J, Miao Z, Ding Y, Xu X, Zhao X, et al. Suppression of the Smurf1 Expression Inhibits Tumor Progression in Gliomas. Cell Mol Neurobiol. 2018;38:421-430 pubmed publisher
    ..b>Smurf1, a member of Nedd4 family of HECT-type ligases, has been reported to contribute to tumorigenicity through several ..
  30. Tajima Y, Goto K, Yoshida M, Shinomiya K, Sekimoto T, Yoneda Y, et al. Chromosomal region maintenance 1 (CRM1)-dependent nuclear export of Smad ubiquitin regulatory factor 1 (Smurf1) is essential for negative regulation of transforming growth factor-beta signaling by Smad7. J Biol Chem. 2003;278:10716-21 pubmed
    Smad ubiquitin regulatory factor 1 (Smurf1), a HECT type E3 ubiquitin ligase, interacts with inhibitory Smad7 and induces translocation of Smad7 to the cytoplasm...
  31. Masumoto K, Kitagawa M. E3 Ubiquitin Ligases as Molecular Targets in Human Oral Cancers. Curr Cancer Drug Targets. 2016;16:130-5 pubmed
    ..Moreover, the HECT-type E3 ligase WWP family and Smurf1 are also involved in the development and growth of human oral cancers...
  32. Shimazu J, Wei J, Karsenty G. Smurf1 Inhibits Osteoblast Differentiation, Bone Formation, and Glucose Homeostasis through Serine 148. Cell Rep. 2016;15:27-35 pubmed publisher
    The E3 ubiquitin ligase Smurf1 targets the master regulator of osteoblast differentiation, Runx2, for degradation, yet the function of Smurf1, if any, during osteoblast differentiation in vivo is ill defined...
  33. Asano Y, Ihn H, Yamane K, Kubo M, Tamaki K. Impaired Smad7-Smurf-mediated negative regulation of TGF-beta signaling in scleroderma fibroblasts. J Clin Invest. 2004;113:253-64 pubmed
    ..There was no significant difference in Smurf1 and Smurf2 levels between normal and scleroderma fibroblasts, and the transiently overexpressed Smurf1 and/or ..
  34. Xu Z, Greenblatt M, Yan G, Feng H, Sun J, Lotinun S, et al. SMURF2 regulates bone homeostasis by disrupting SMAD3 interaction with vitamin D receptor in osteoblasts. Nat Commun. 2017;8:14570 pubmed publisher
    ..Furthermore, the bone mass phenotype in Smurf2- and Smurf1-deficient mice is opposite, indicating that SMURF2 has a non-overlapping and, in some respects, opposite function ..
  35. Dalbo V, Roberts M, Hassell S, Kerksick C. Effects of pre-exercise feeding on serum hormone concentrations and biomarkers of myostatin and ubiquitin proteasome pathway activity. Eur J Nutr. 2013;52:477-87 pubmed publisher
    ..changes in myostatin (MSTN), activin IIB, follistatin-like 3 (FSTL3), SMAD specific E3 ubiquitin protein ligase 1 (SMURF1), forkhead box O3, F-box protein 32 (FBXO32), and Muscle RING-finger protein-1, with beta-actin serving as the ..
  36. Tang X, Chen X, Xu Y, Qiao Y, Zhang X, Wang Y, et al. CD166 positively regulates MCAM via inhibition to ubiquitin E3 ligases Smurf1 and βTrCP through PI3K/AKT and c-Raf/MEK/ERK signaling in Bel-7402 hepatocellular carcinoma cells. Cell Signal. 2015;27:1694-702 pubmed publisher
    ..Mechanically, CD166 down-regulated two ubiquitin E3 ligases, βTrCP and Smurf1, which play critical roles in the destability of MCAM protein...
  37. Elkouris M, Kontaki H, Stavropoulos A, Antonoglou A, Nikolaou K, Samiotaki M, et al. SET9-Mediated Regulation of TGF-? Signaling Links Protein Methylation to Pulmonary Fibrosis. Cell Rep. 2016;15:2733-44 pubmed publisher
    ..These results uncover a complex regulatory interplay among multiple Smad7 modifications and highlight the possibility that protein methyltransferases may represent promising therapeutic targets for treating lung fibrosis. ..
  38. Lee Y, Park J, Kim J, Jung S, Lee J, Kim S, et al. Smad6-specific recruitment of Smurf E3 ligases mediates TGF-?1-induced degradation of MyD88 in TLR4 signalling. Nat Commun. 2011;2:460 pubmed publisher
    ..on the Smad6 protein, but not Smad7, and mediated by recruitment of the Smad ubiquitin regulator factor proteins, Smurf1 and Smurf2, which have E3-ubiquitin ligase activity...
  39. Sun X, Xie Z, Ma Y, Pan X, Wang J, Chen Z, et al. TGF-? inhibits osteogenesis by upregulating the expression of ubiquitin ligase SMURF1 via MAPK-ERK signaling. J Cell Physiol. 2018;233:596-606 pubmed publisher
    ..Western blotting analysis indicated that TGF-? induced protein expression of E3 ubiquitin-protein ligase SMURF1, which contributed to the degradation of RUNX2 and SMAD1 as evidenced by SMURF1 inhibition using RNA interference ..
  40. Wei X, Wang X, Zhan J, Chen Y, Fang W, Zhang L, et al. Smurf1 inhibits integrin activation by controlling Kindlin-2 ubiquitination and degradation. J Cell Biol. 2017;216:1455-1471 pubmed publisher
    ..Here, we demonstrate that the E3 ubiquitin ligase Smurf1 controls the amount of Kindlin-2 protein in cells and hinders integrin activation...
  41. Tao Y, Sun C, Zhang T, Song Y. SMURF1 promotes the proliferation, migration and invasion of gastric cancer cells. Oncol Rep. 2017;38:1806-1814 pubmed publisher
    Smad ubiquitin regulatory factor 1 (SMURF1), a well-known E3 ubiquitin ligase, targets substrate proteins for ubiquitination and proteasomal degradation...
  42. Franco L, Nair V, Scharn C, Xavier R, Torrealba J, Shiloh M, et al. The Ubiquitin Ligase Smurf1 Functions in Selective Autophagy of Mycobacterium tuberculosis and Anti-tuberculous Host Defense. Cell Host Microbe. 2017;21:59-72 pubmed publisher
    ..b>Smurf1 is an E3 ubiquitin ligase whose role in selective bacterial autophagy is unknown...
  43. Liu J, Liang C, Guo B, Wu X, Li D, Zhang Z, et al. Increased PLEKHO1 within osteoblasts suppresses Smad-dependent BMP signaling to inhibit bone formation during aging. Aging Cell. 2017;16:360-376 pubmed publisher
    ..ubiquitination-related molecule that could specifically target the linker region between the WW domains of Smurf1 to promote the ubiquitination of Smad1/5...
  44. Lian C, Wu Z, Gao B, Peng Y, Liang A, Xu C, et al. Melatonin reversed tumor necrosis factor-alpha-inhibited osteogenesis of human mesenchymal stem cells by stabilizing SMAD1 protein. J Pineal Res. 2016;61:317-27 pubmed publisher
    ..melatonin rescued TNF?-inhibited osteogenesis of human mesenchymal stem cells and that the interactions between SMURF1 and SMAD1 mediated the crosstalk between melatonin signaling and TNF? signaling...
  45. Tovar Vidales T, Fitzgerald A, Clark A. Human trabecular meshwork cells express BMP antagonist mRNAs and proteins. Exp Eye Res. 2016;147:156-160 pubmed publisher
    ..whether cultured human TM cells: (a) express other BMP antagonists including noggin, chordin, BMPER, BAMBI, Smurf1 and 2, and (b) whether expression of these proteins is regulated by exogenous TGF-β2 treatment...
  46. Wang X, Zhang H, Hu Y, Zong Z, Li Y, Li C. [The role of Smad ubiquitination regulatory factor 1 in hepatocellular carcinoma]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2012;29:533-6 pubmed publisher
    To determine the expression level of Smad ubiquitination regulatory factor 1 (SMURF1) gene in hepatocellular carcinoma, and to explore its role in liver cancer...
  47. Wang Z, Wang J, Li X, Xing L, Ding Y, Shi P, et al. Bortezomib prevents oncogenesis and bone metastasis of prostate cancer by inhibiting WWP1, Smurf1 and Smurf2. Int J Oncol. 2014;45:1469-78 pubmed publisher
    ..To explore activities of the ubiquitin ligase E3s WWP1, Smurf1 and Smurf2 in oncogenesis and bone metastasis of prostate cancer, as well as in the functional mechanism of ..
  48. Li S, Lu K, Wang J, An L, Yang G, Chen H, et al. Ubiquitin ligase Smurf1 targets TRAF family proteins for ubiquitination and degradation. Mol Cell Biochem. 2010;338:11-7 pubmed publisher
    The HECT-type E3 Smad ubiquitination regulation factor 1 (Smurf1) functions in regulation of cell polarity and bone homeostasis by targeting Smads, Runx2, RhoA and MEKK2 for ubiquitination and degradation...
  49. Lin H, Ying Y, Wang Y, Wang G, Jiang S, Huang D, et al. AMPK downregulates ALK2 via increasing the interaction between Smurf1 and Smad6, leading to inhibition of osteogenic differentiation. Biochim Biophys Acta Mol Cell Res. 2017;1864:2369-2377 pubmed publisher
    ..Furthermore, activation of AMPK upregulated Smad6 and Smurf1 and thereby enhanced their interactions, resulting in its proteosome-dependent degradation of ALK2...
  50. Zhang M, Zhang W, Tan J, Zhao M, Lian L, Cai J. Poly r(C) binding protein (PCBP) 1 expression is regulated by the E3 ligase UBE4A in thyroid carcinoma. Biosci Rep. 2017;37: pubmed publisher
    ..Low UBE4A expression level was associated with a better prognosis in thyroid cancer patients. Our data reveal a post-translational regulatory mechanism of regulating PCBP1 expression in thyroid cancer cells. ..
  51. Sangadala S, Rao Metpally R, B Reddy B. Molecular Interaction Between Smurfl WW2 Domain and PPXY Motifs of Smadl, Smad5, and Smad6-Modeling and Analysis. J Biomol Struct Dyn. 2007;25:11-23 pubmed
    ..R-Smads contain PPXY motif in the linker region that interacts with Smad ubiquitin regulatory factor 1 (Smurf1), an E3 ubiquitin ligase that catalyzes ubiquitination of target proteins for proteasomal degradation...
  52. Hwang Y, Lee H, Kamata T, Mood K, Cho H, Winterbottom E, et al. The Smurf ubiquitin ligases regulate tissue separation via antagonistic interactions with ephrinB1. Genes Dev. 2013;27:491-503 pubmed publisher
    ..EphrinB1 is targeted by Smurf2 for degradation; however, a Smurf1 interaction with ephrinB1 prevents the association with Smurf2 and precludes ephrinB1 from ubiquitination and ..
  53. Fei C, He X, Xie S, Miao H, Zhou Z, Li L. Smurf1-mediated axin ubiquitination requires Smurf1 C2 domain and is cell cycle-dependent. J Biol Chem. 2014;289:14170-7 pubmed publisher
    Previously, Smad ubiquitination regulatory factor 1 (Smurf1)-mediated Lys29 (K29)-linked poly-ubiquitination of Axin has been identified as a novel regulatory process in Wnt/?-catenin signaling...
  54. Zhang W, Zhuang Y, Zhang Y, Yang X, Zhang H, Wang G, et al. Uev1A facilitates osteosarcoma differentiation by promoting Smurf1-mediated Smad1 ubiquitination and degradation. Cell Death Dis. 2017;8:e2974 pubmed publisher
    ..Uev1A appears to be involved in the BMP signaling pathway in which it collaborates with a ubiquitin E3 ligase Smurf1 to promote Smad1 degradation in a Ubc13-independent manner...
  55. Anindya R, Aygün O, Svejstrup J. Damage-induced ubiquitylation of human RNA polymerase II by the ubiquitin ligase Nedd4, but not Cockayne syndrome proteins or BRCA1. Mol Cell. 2007;28:386-97 pubmed
    ..Nedd4-dependent RNAPII ubiquitylation could also be reconstituted with highly purified proteins. Together, our results indicate that transcriptional arrest at DNA lesions triggers Nedd4 recruitment and RNAPII ubiquitylation. ..
  56. Yoo J, Lim T, Park J, Hah Y, Park N, Hong S, et al. SYT14L, especially its C2 domain, is involved in regulating melanocyte differentiation. J Dermatol Sci. 2013;72:246-51 pubmed publisher
    ..These results suggest that SYT14L, especially its C2 domain, may play an important role in regulating melanocyte differentiation through the modulation of ERK and (or) CREB signaling. ..
  57. Kwon A, Lee H, Woo K, Ryoo H, Baek J. SMURF1 plays a role in EGF-induced breast cancer cell migration and invasion. Mol Cells. 2013;36:548-55 pubmed publisher
    ..Previous studies have shown that SMAD ubiquitination regulatory factor 1 (SMURF1), an E3 ubiquitin ligase, regulates cell motility by inducing RhoA degradation...
  58. Haag J, Chubinskaya S, Aigner T. Hgs physically interacts with Smad5 and attenuates BMP signaling. Exp Cell Res. 2006;312:1153-63 pubmed
    ..Thus, it is tempting to speculate that both might be related to each other given the suppressive effect of BMP signaling on Hgs shown in this study. ..
  59. Al Salihi M, Herhaus L, MacArtney T, Sapkota G. USP11 augments TGFβ signalling by deubiquitylating ALK5. Open Biol. 2012;2:120063 pubmed publisher
    ..Central to TGFβ pathway signalling in early embryogenesis and carcinogenesis is TGFβ-induced epithelial to mesenchymal transition. USP11 depletion results in inhibition of TGFβ-induced epithelial to mesenchymal transition. ..
  60. Boonanantanasarn K, Lee H, Baek K, Woo K, Ryoo H, Baek J, et al. EGF Inhibits Wnt/β-Catenin-Induced Osteoblast Differentiation by Promoting β-Catenin Degradation. J Cell Biochem. 2015;116:2849-57 pubmed publisher
    ..we demonstrated that epidermal growth factor (EGF) inhibits BMP2-induced osteoblast differentiation by inducing Smurf1 expression...
  61. Qian G, Ren Y, Zuo Y, Yuan Y, Zhao P, Wang X, et al. Smurf1 represses TNF-? production through ubiquitination and destabilization of USP5. Biochem Biophys Res Commun. 2016;474:491-496 pubmed publisher
    ..Here we found that Smad ubiquitination regulatory factor 1 (Smurf1) down regulated protein expression of USP5, and the E3 enzyme activity of Smurf1 was ..
  62. Aragon E, Goerner N, Xi Q, Gomes T, Gao S, Massague J, et al. Structural basis for the versatile interactions of Smad7 with regulator WW domains in TGF-? Pathways. Structure. 2012;20:1726-36 pubmed publisher
    ..The transcription coactivator YAP and the E3 ubiquitin ligases Smurf1/2 and Nedd4L target R-Smads for activation or degradation, respectively...
  63. Zhou T, Liang B, Su G, Gong W, Li H, Tian L, et al. Identification of ubiquitin target proteins using cell-based arrays. J Proteome Res. 2007;6:4397-406 pubmed
    ..Therefore, the technique utilized here will facilitate future research on ubiquitination-regulated cell signaling. ..
  64. Makioka K, Yamazaki T, Takatama M, Ikeda M, Okamoto K. Immunolocalization of Smurf1 in Hirano bodies. J Neurol Sci. 2014;336:24-8 pubmed publisher
    The Smad ubiquitination regulatory factor 1 (Smurf1) is one of the E3 ubiquitin ligases and is related to multiple biological processes...
  65. Chan W, Tian R, Lee Y, Sit S, Lim L, Manser E. Down-regulation of active ACK1 is mediated by association with the E3 ubiquitin ligase Nedd4-2. J Biol Chem. 2009;284:8185-94 pubmed publisher
    ..These processes are particularly pertinent given the report of genomic amplification of the ACK1 locus in metastatic tumors. ..
  66. Le Scolan E, Zhu Q, Wang L, Bandyopadhyay A, Javelaud D, Mauviel A, et al. Transforming growth factor-beta suppresses the ability of Ski to inhibit tumor metastasis by inducing its degradation. Cancer Res. 2008;68:3277-85 pubmed publisher
    ..Our results suggest that the ability of TGF-beta to induce degradation of Ski could be an additional mechanism contributing to its protumorigenic activity. ..
  67. Crose L, Hilder T, Sciaky N, Johnson G. Cerebral cavernous malformation 2 protein promotes smad ubiquitin regulatory factor 1-mediated RhoA degradation in endothelial cells. J Biol Chem. 2009;284:13301-5 pubmed publisher
    ..we define a novel mechanism where the CCM2 phosphotyrosine binding (PTB) domain binds the ubiquitin ligase (E3) Smurf1, controlling RhoA degradation...
  68. Yang F, Xu N, Li D, Guan L, He Y, Zhang Y, et al. A feedback loop between RUNX2 and the E3 ligase SMURF1 in regulation of differentiation of human dental pulp stem cells. J Endod. 2014;40:1579-86 pubmed publisher
    ..Smad ubiquitylation regulatory factor-1 (SMURF1) promotes RUNX2 degradation and negatively regulates osteoblast differentiation, whereas RUNX2 activates SMURF1 ..
  69. Wang Y, Tong X, Ye X. Ndfip1 negatively regulates RIG-I-dependent immune signaling by enhancing E3 ligase Smurf1-mediated MAVS degradation. J Immunol. 2012;189:5304-13 pubmed publisher
    ..Further analysis indicated that Ndfip1 enhances both self-ubiquitination of HECT domain-containing E3 ubiquitin ligase Smurf1 and its interaction with MAVS, and eventually promotes MAVS degradation...
  70. Lee M, Jeong S, Ko K, Park S, Ryu B, Kim I, et al. RASSF1A Directly Antagonizes RhoA Activity through the Assembly of a Smurf1-Mediated Destruction Complex to Suppress Tumorigenesis. Cancer Res. 2016;76:1847-59 pubmed publisher
    ..interaction between the N-terminal amino acids (69-82) of RASSF1A and the ubiquitin E3 ligase Smad ubiquitination regulatory factor 1 (Smurf1) disrupted GTPase activity by facilitating Smurf1-mediated ubiquitination of GTP-RhoA...
  71. Boyer L, Turchi L, Desnues B, Doye A, Ponzio G, Mege J, et al. CNF1-induced ubiquitylation and proteasome destruction of activated RhoA is impaired in Smurf1-/- cells. Mol Biol Cell. 2006;17:2489-97 pubmed
    ..the relationship between permanent activation of RhoA catalyzed by CNF1 and subsequent ubiquitylation of RhoA by Smurf1. Using Smurf1-deficient cells and by RNA interference (RNAi)-mediated Smurf1 knockdown, we demonstrate that Smurf1 ..
  72. Salah Z, Cohen S, Itzhaki E, Aqeilan R. NEDD4 E3 ligase inhibits the activity of the Hippo pathway by targeting LATS1 for degradation. Cell Cycle. 2013;12:3817-23 pubmed publisher
    ..These findings might be applied in the development of new therapeutic approaches through the activation of LATS1. ..