SMURF2

Summary

Gene Symbol: SMURF2
Description: SMAD specific E3 ubiquitin protein ligase 2
Alias: E3 ubiquitin-protein ligase SMURF2, E3 ubiquitin ligase SMURF2, HECT-type E3 ubiquitin transferase SMURF2, SMAD ubiquitination regulatory factor 2, hSMURF2
Species: human
Products:     SMURF2

Top Publications

  1. Lee Y, Han J, Son S, Choi J, Jeon E, Bae S, et al. AIMP1/p43 downregulates TGF-beta signaling via stabilization of smurf2. Biochem Biophys Res Commun. 2008;371:395-400 pubmed publisher
    ..Here, we report that AIMP1 negatively regulates TGF-beta signaling via stabilization of Smurf2. TGF-beta-dependent phosphorylation and nuclear localization of R-Smads, induction of target genes, and growth ..
  2. Ogunjimi A, Briant D, Pece Barbara N, Le Roy C, Di Guglielmo G, Kavsak P, et al. Regulation of Smurf2 ubiquitin ligase activity by anchoring the E2 to the HECT domain. Mol Cell. 2005;19:297-308 pubmed
    ..In TGFbeta signaling the inhibitory protein Smad7 recruits Smurf2, an E3 of the C2-WW-HECT domain class, to the TGFbeta receptor complex to facilitate receptor degradation...
  3. 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 through ..
  4. 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
    ..Previously identified as a regulator of renal sodium channels, Nedd4L is shown here to play a broader role as a general modulator of Smad turnover during TGF-beta signal transduction. ..
  5. Li H, Seth A. An RNF11: Smurf2 complex mediates ubiquitination of the AMSH protein. Oncogene. 2004;23:1801-8 pubmed
    ..Previously, we have shown that RNF11 interacts with the HECT-type E3 ligases AIP4 and Smurf2. Here, we show that RNF11 binds to AMSH in mammalian cells and that this interaction is independent of the RNF11 ..
  6. Zhang H, Cohen S. Smurf2 up-regulation activates telomere-dependent senescence. Genes Dev. 2004;18:3028-40 pubmed
    ..Here we report that up-regulation of Smurf2, an E3 ubiquitin ligase previously implicated in TGF-beta signaling, is a specific consequence of telomere ..
  7. Zhang H, Teng Y, Kong Y, Kowalski P, Cohen S. Suppression of human tumor cell proliferation by Smurf2-induced senescence. J Cell Physiol. 2008;215:613-20 pubmed publisher
    ..The E3 ubiquitin ligase Smurf2 is up-regulated during replicative senescence in response to telomere shortening, and induces senescence ..
  8. 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
    ..To our knowledge, this is the first report to demonstrate that Smurf1/2 functions as a factor to stabilize MDM2 protein rather than as a direct E3 ligase in regulation of p53 degradation. ..
  9. Subramaniam V, Li H, Wong M, Kitching R, Attisano L, Wrana J, et al. The RING-H2 protein RNF11 is overexpressed in breast cancer and is a target of Smurf2 E3 ligase. Br J Cancer. 2003;89:1538-44 pubmed
    ..the PPPPY sequence of RNF11 PY motif is identical to that of Smad7, which has been shown to bind to WW domains of Smurf2, an E3 ubiquitin ligase that mediates the ubiquitination and degradation of the TGFbeta receptor complex...

More Information

Publications144 found, 100 shown here

  1. Blank M, Tang Y, Yamashita M, Burkett S, Cheng S, Zhang Y. A tumor suppressor function of Smurf2 associated with controlling chromatin landscape and genome stability through RNF20. Nat Med. 2012;18:227-34 pubmed publisher
    ..Here we show that genomic ablation of Smad ubiquitin regulatory factor 2 (Smurf2), a HECT-domain E3 ubiquitin ligase, results in dysregulation of both the DNA damage response and genomic ..
  2. Bonni S, Wang H, Causing C, Kavsak P, Stroschein S, Luo K, et al. TGF-beta induces assembly of a Smad2-Smurf2 ubiquitin ligase complex that targets SnoN for degradation. Nat Cell Biol. 2001;3:587-95 pubmed
    ..of TGF-beta signalling, Smad2 interacts through its proline-rich PPXY motif with the tryptophan-rich WW domains of Smurf2, a recently identified E3 ubiquitin ligases...
  3. Wu Q, Huang J, Sampson E, Kim K, Zuscik M, O Keefe R, et al. Smurf2 induces degradation of GSK-3beta and upregulates beta-catenin in chondrocytes: a potential mechanism for Smurf2-induced degeneration of articular cartilage. Exp Cell Res. 2009;315:2386-98 pubmed publisher
    We have previously demonstrated that Smurf2 is highly expressed in human osteoarthritis (OA) tissue, and overexpression of Smurf2 under the control of the type II collagen promoter (Col2a1) induces an OA-like phenotype in aged Col2a1-..
  4. Kong Y, Cui H, Zhang H. Smurf2-mediated ubiquitination and degradation of Id1 regulates p16 expression during senescence. Aging Cell. 2011;10:1038-46 pubmed publisher
    ..Here, we report for the first time the identification of Smurf2 as the E3 ligase that ubiquitinates Id1 and Id3...
  5. 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
    ..In this study, we have identified a novel HECT class ubiquitin E3 ligase, designated Smurf2, that negatively regulates Smad2 signaling...
  6. Jin C, Yang Y, Anver M, Morris N, Wang X, Zhang Y. Smad ubiquitination regulatory factor 2 promotes metastasis of breast cancer cells by enhancing migration and invasiveness. Cancer Res. 2009;69:735-40 pubmed publisher
    ..Dysregulation of the UPS often accompanies tumorigenesis and progression. Here, we report that Smad ubiquitination regulatory factor 2 (Smurf2), a HECT-domain containing E3 ubiquitin ligase, is up-regulated in certain breast cancer ..
  7. 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...
  8. 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
    ..Here, we report the identification of Smurf2, a new member of the Hect family of E3 ubiquitin ligases...
  9. Kavsak P, Rasmussen R, Causing C, Bonni S, Zhu H, Thomsen G, et al. Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF beta receptor for degradation. Mol Cell. 2000;6:1365-75 pubmed
    Ubiquitin-mediated proteolysis regulates the activity of diverse receptor systems. Here, we identify Smurf2, a C2-WW-HECT domain ubiquitin ligase and show that Smurf2 associates constitutively with Smad7...
  10. Osmundson E, Ray D, Moore F, Gao Q, Thomsen G, Kiyokawa H. The HECT E3 ligase Smurf2 is required for Mad2-dependent spindle assembly checkpoint. J Cell Biol. 2008;183:267-77 pubmed publisher
    ..In this study, we demonstrate that a HECT (homologous to the E6-AP carboxyl terminus) ubiquitin ligase, Smurf2, is required for the spindle checkpoint. Smurf2 localizes to the centrosome, mitotic midbody, and centromeres...
  11. Ray D, Ahsan A, Helman A, Chen G, Hegde A, Gurjar S, et al. Regulation of EGFR protein stability by the HECT-type ubiquitin ligase SMURF2. Neoplasia. 2011;13:570-8 pubmed
    ..Here, we report a novel interaction of EGFR with an HECT-type ubiquitin ligase SMURF2, which can ubiquitinate, but stabilize EGFR by protecting it from c-Cbl-mediated degradation...
  12. Tang L, Yamashita M, Coussens N, Tang Y, Wang X, Li C, et al. Ablation of Smurf2 reveals an inhibition in TGF-β signalling through multiple mono-ubiquitination of Smad3. EMBO J. 2011;30:4777-89 pubmed publisher
    ..Here, we generated mice harbouring a target-disrupted Smurf2 allele...
  13. Jin Y, Jeon E, Li Q, Lee Y, Choi J, Kim W, et al. Transforming growth factor-beta stimulates p300-dependent RUNX3 acetylation, which inhibits ubiquitination-mediated degradation. J Biol Chem. 2004;279:29409-17 pubmed
    ..Our findings demonstrate that the level of RUNX3 protein is controlled by the competitive acetylation and deacetylation of the three lysine residues, revealing a new mechanism for the posttranslational regulation of RUNX3 expression. ..
  14. Eichhorn P, Rodón L, Gonzàlez Juncà A, Dirac A, Gili M, Martínez Sáez E, et al. USP15 stabilizes TGF-? receptor I and promotes oncogenesis through the activation of TGF-? signaling in glioblastoma. Nat Med. 2012;18:429-35 pubmed publisher
    ..USP15 binds to the SMAD7-SMAD specific E3 ubiquitin protein ligase 2 (SMURF2) complex and deubiquitinates and stabilizes type I TGF-? receptor (T?R-I), leading to an enhanced TGF-? signal...
  15. Emanuelli A, Manikoth Ayyathan D, Koganti P, Shah P, Apel Sarid L, Paolini B, et al. Altered Expression and Localization of Tumor Suppressive E3 Ubiquitin Ligase SMURF2 in Human Prostate and Breast Cancer. Cancers (Basel). 2019;11: pubmed publisher
    b>SMURF2, an E3 ubiquitin ligase and suggested tumor suppressor, operates in normal cells to prevent genomic instability and carcinogenesis...
  16. Hu P, Nebreda A, Hanenberg H, Kinnebrew G, Ivan M, Yoder M, et al. P38α/JNK signaling restrains erythropoiesis by suppressing Ezh2-mediated epigenetic silencing of Bim. Nat Commun. 2018;9:3518 pubmed publisher
    ..JNK prevents Cdk1-mediated phosphorylation and subsequent degradation by Smurf2 of the epigenetic silencer Ezh2. Stabilized Ezh2 silences Bim expression and protects erythroblasts from apoptosis...
  17. Kim J, Ham S, Lee Y, Suh G, Lee Y. TTC3 contributes to TGF-β1-induced epithelial-mesenchymal transition and myofibroblast differentiation, potentially through SMURF2 ubiquitylation and degradation. Cell Death Dis. 2019;10:92 pubmed publisher
    ..SMAD-specific ubiquitin E3 ligase (SMAD ubiquitination regulatory factor 2, SMURF2) controls TGF-β signaling proteins including the TGF-β receptor (TGFR) and SMAD2/3...
  18. Yu L, Dong L, Wang Y, Liu L, Long H, Li H, et al. Reversible regulation of SATB1 ubiquitination by USP47 and SMURF2 mediates colon cancer cell proliferation and tumor progression. Cancer Lett. 2019;448:40-51 pubmed publisher
    ..Furthermore, we identified SMURF2 as an E3 ubiquitin ligase that promotes SATB1 degradation by upregulating its ubiquitination, and its deficiency ..
  19. Teyra J, Singer A, Schmitges F, Jaynes P, Kit Leng Lui S, Polyak M, et al. Structural and Functional Characterization of Ubiquitin Variant Inhibitors of USP15. Structure. 2019;27:590-605.e5 pubmed publisher
    ..In cells, the UbVs inhibited the deubiquitination of two USP15 substrates, SMURF2 and TRIM25, and the diUbV inhibited the effects of USP15 on the transforming growth factor β pathway...
  20. Sreekumar V, Aspera Werz R, Tendulkar G, Reumann M, Freude T, Breitkopf Heinlein K, et al. BMP9 a possible alternative drug for the recently withdrawn BMP7? New perspectives for (re-)implementation by personalized medicine. Arch Toxicol. 2017;91:1353-1366 pubmed publisher
    ..Smad4 and RANKL, while the response of rhBMP9 correlated to the expression levels of Alk6, Endoglin, Smurf1, Smurf2, SOST and RANKL in these donors...
  21. Wang J, Li H, Wang H, Su Z. MicroRNA-485 Modulates the TGF-β/ Smads Signaling Pathway in Chronic Asthmatic Mice by Targeting Smurf2. Cell Physiol Biochem. 2018;51:692-710 pubmed publisher
    ..ASMCs were transfected with miR-485 mimic, miR-485 inhibitor and siRNA-Smurf2. The reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analyses were applied ..
  22. 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. ..
  23. Huang H, Veien E, Zhang H, Ayers D, Song J. Skeletal Characterization of Smurf2-Deficient Mice and In Vitro Analysis of Smurf2-Deficient Chondrocytes. PLoS ONE. 2016;11:e0148088 pubmed publisher
    Overexpression of Smad ubiquitin regulatory factor 2 (Smurf2) in chondrocytes was reported to cause spontaneous osteoarthritis (OA) in mice...
  24. Wang Y, Xiao Y, Li S, Shi L, Liu L, Zhang Y, et al. BMP-7 enhances SnoN mRNA expression in renal tubular epithelial cells under high-glucose conditions. Mol Med Rep. 2017;16:3308-3314 pubmed publisher
    ..progression of DN, the expression of BMP‑7 in rat renal tissue was downregulated, whereas the expression of Smurf2 and Arkadia increased...
  25. Borgo C, Vilardell J, Bosello Travain V, Pinna L, Venerando A, Salvi M. Dependence of HSP27 cellular level on protein kinase CK2 discloses novel therapeutic strategies. Biochim Biophys Acta Gen Subj. 2018;1862:2902-2910 pubmed publisher
    ..is able to regulate HSP27 turnover by affecting the expression of its ubiquitin ligase SMURF2 (Smad ubiquitination regulatory factor 2)...
  26. Chang H, Lin Y, Tsai P, Liang C, Yan Y. The FYVE domain of Smad Anchor for Receptor Activation (SARA) is required to prevent skin carcinogenesis, but not in mouse development. PLoS ONE. 2014;9:e105299 pubmed publisher
    ..The decreasing expression of Smad2 was caused by enhancing Smurf2-mediated proteasome degradation pathway...
  27. Toofan P, Busch C, Morrison H, O Brien S, Jørgensen H, Copland M, et al. Chronic myeloid leukaemia cells require the bone morphogenic protein pathway for cell cycle progression and self-renewal. Cell Death Dis. 2018;9:927 pubmed publisher
    ..was significant deregulation of several genes involved in the BMP pathway with ACV1C, INHBA, SMAD7, SNAIL1 and SMURF2 showing differential expression in relation to response...
  28. Wu Q, Chen D, Zuscik M, O Keefe R, Rosier R. Overexpression of Smurf2 stimulates endochondral ossification through upregulation of beta-catenin. J Bone Miner Res. 2008;23:552-63 pubmed
    Ectopic expression of Smurf2 in chondrocytes and perichondrial cells accelerated endochondral ossification by stimulating chondrocyte maturation and osteoblast development through upregulation of beta-catenin in Col2a1-Smurf2 embryos...
  29. Cui X, Sun X, Lu F, Jiang X. Baicalein represses TGF-β1-induced fibroblast differentiation through the inhibition of miR-21. Toxicol Appl Pharmacol. 2018;358:35-42 pubmed publisher
    ..the expression of Spry 1 protein, a miR-21 known target, was improved by baicalein treatment, but the level of Smurf2 protein, another miR-21 target, was not interfered...
  30. He L, Yang N, Isales C, Shi X. Glucocorticoid-induced leucine zipper (GILZ) antagonizes TNF-α inhibition of mesenchymal stem cell osteogenic differentiation. PLoS ONE. 2012;7:e31717 pubmed publisher
    ..TNF-α also induces the expression of E3 ubiquitin ligase protein Smurf1 and Smurf2 and promotes degradation of Runx2, another key transcription factor regulating osteoblast differentiation and bone ..
  31. Liu X, Gu X, Sun L, Flowers A, Rademaker A, Zhou Y, et al. Downregulation of Smurf2, a tumor-suppressive ubiquitin ligase, in triple-negative breast cancers: involvement of the RB-microRNA axis. BMC Cancer. 2014;14:57 pubmed publisher
    The HECT family ubiquitin ligase Smurf2 regulates cell polarity, migration, division, differentiation and death, by targeting diverse substrates that are critical for receptor signaling, cytoskeleton, chromatin remodeling and ..
  32. Mund T, Lewis M, Maslen S, Pelham H. Peptide and small molecule inhibitors of HECT-type ubiquitin ligases. Proc Natl Acad Sci U S A. 2014;111:16736-41 pubmed publisher
    ..5(7):502-507] can target the E2 binding sites on the HECT domains of Smurf2, Nedd4, Mule/Huwe1, and WWP1, and thus act as specific inhibitors of these enzymes in vitro...
  33. Wu B, Guo B, Kang J, Deng X, Fan Y, Zhang X, et al. Downregulation of Smurf2 ubiquitin ligase in pancreatic cancer cells reversed TGF-?-induced tumor formation. Tumour Biol. 2016;: pubmed
    Smad ubiquitin regulatory factor 2 (Smurf2) is an E3 ubiquitin ligase that regulates transforming growth factor ? (TGF-?)/Smad signaling and is implicated in a wide range of cellular responses...
  34. Hausmann M, Ilic N, Pilarczyk G, Lee J, Logeswaran A, Borroni A, et al. Challenges for Super-Resolution Localization Microscopy and Biomolecular Fluorescent Nano-Probing in Cancer Research. Int J Mol Sci. 2017;18: pubmed publisher
    ..re-arrangements of Erb-receptors in membranes, spatial organization of Smad specific ubiquitin protein ligase 2 (Smurf2) in the cytosol, tumor cell characteristic heterochromatin organization, and molecular re-arrangements induced by ..
  35. 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. ..
  36. Runyan C, Hayashida T, Hubchak S, Curley J, Schnaper H. Role of SARA (SMAD anchor for receptor activation) in maintenance of epithelial cell phenotype. J Biol Chem. 2009;284:25181-9 pubmed publisher
    ..However, the ubiquitination of Smad2 is increased in SARA-deficient cells. We therefore examined the E3 ubiquitin ligase Smurf2 and found that although Smurf2 expression was unaltered in SARA-deficient cells, the interaction of ..
  37. Santonico E, Belleudi F, Panni S, Torrisi M, Cesareni G, Castagnoli L. Multiple modification and protein interaction signals drive the Ring finger protein 11 (RNF11) E3 ligase to the endosomal compartment. Oncogene. 2010;29:5604-18 pubmed publisher
  38. Qureshi M, Jabeen S, Butt G, Aslam A, Naqvi S, Attar R, et al. Tudor tells about new twists in the story tale of SMURFs. Cell Mol Biol (Noisy-le-grand). 2016;62:38-43 pubmed
    ..This family has two members, SMURF1 and SMURF2. SMURFs have emerged as well studied negative regulators of TGF induced intracellular signaling...
  39. Iezaki T, Fukasawa K, Horie T, Park G, Robinson S, Nakaya M, et al. The MAPK Erk5 is necessary for proper skeletogenesis involving a Smurf-Smad-Sox9 molecular axis. Development. 2018;145: pubmed publisher
    ..We further demonstrate that Erk5 directly phosphorylates and activates Smurf2 (a ubiquitin E3 ligase) at Thr249, which promotes the proteasomal degradation of Smad proteins and ..
  40. 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. ..
  41. Liu J, Li X, Zhang H, Gu R, Wang Z, Gao Z, et al. Ubiquitin E3 ligase Itch negatively regulates osteoblast function by promoting proteasome degradation of osteogenic proteins. Bone Joint Res. 2017;6:154-161 pubmed publisher
    ..1 (Wwp1), SMAD Specific E3 Ubiquitin Protein Ligase 1 (Smurf1), SMAD Specific E3 Ubiquitin Protein Ligase 2 (Smurf2) and Itch were all significantly increased in the fracture callus of WT mice, which was associated with elevated ..
  42. David D, Surendran A, Thulaseedharan J, Nair A. Regulation of CNKSR2 protein stability by the HECT E3 ubiquitin ligase Smurf2, and its role in breast cancer progression. BMC Cancer. 2018;18:284 pubmed publisher
    b>Smurf2 E3 ubiquitin ligase physically associates with and regulate the stability of distinct cellular protein substrates...
  43. Chong P, Lin H, Wrana J, Forman Kay J. Coupling of tandem Smad ubiquitination regulatory factor (Smurf) WW domains modulates target specificity. Proc Natl Acad Sci U S A. 2010;107:18404-9 pubmed publisher
    b>Smad ubiquitination regulatory factor 2 (Smurf2) is an E3 ubiquitin ligase that participates in degradation of TGF-? receptors and other targets...
  44. Lin T, Gibon E, Loi F, Pajarinen J, Córdova L, Nabeshima A, et al. Decreased osteogenesis in mesenchymal stem cells derived from the aged mouse is associated with enhanced NF-?B activity. J Orthop Res. 2017;35:281-288 pubmed publisher
    ..Both Smurf2 and TAZ, the NF-?B target genes that regulate osteogenic differentiation, were increased in aged MSCs...
  45. Tan Y, Chen Y, Du M, Peng Z, Xie P. USF2 inhibits the transcriptional activity of Smurf1 and Smurf2 to promote breast cancer tumorigenesis. Cell Signal. 2019;53:49-58 pubmed publisher
    Smurf1 (Smad ubiquitylation regulatory factor 1) and Smurf2 are negative regulators of the TGF-β (transforming growth factor-β) pathway. The protein stability and ubiquitin E3 activity regulation of Smurfs have been well studied...
  46. Kristariyanto Y, Choi S, Rehman S, Ritorto M, Campbell D, Morrice N, et al. Assembly and structure of Lys33-linked polyubiquitin reveals distinct conformations. Biochem J. 2015;467:345-52 pubmed publisher
    ..Importantly, our work provides a method to assemble Lys33-linked polyUb that will allow further characterization of this atypical chain type. ..
  47. Zhang W, Zhang J, Wu X, Yan T, Lv W. miR-15b promotes epithelial-mesenchymal transition by inhibiting SMURF2 in pancreatic cancer. Int J Oncol. 2015;47:1043-53 pubmed publisher
    ..We report here that silencing SMURF2 (SMAD specific E3 ubiquitin protein ligase 2) promoted EMT in HPDE6c7 normal pancreas cells and overexpression of ..
  48. Kit Leng Lui S, Iyengar P, Jaynes P, Isa Z, Pang B, Tan T, et al. USP26 regulates TGF-β signaling by deubiquitinating and stabilizing SMAD7. EMBO Rep. 2017;18:797-808 pubmed publisher
    ..SMAD7, a direct transcriptional target of downstream TGF-β signaling acts as a scaffold to recruit the E3 ligase SMURF2 to target the TGF-β receptor complex for ubiquitin-mediated degradation...
  49. 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 Smurf2 did not ..
  50. Ganji A, Roshan H, Varasteh A, Moghadam M, Sankian M. The effects of WW2/WW3 domains of Smurf2 molecule on TGF-β signaling and arginase I gene expression. Cell Biol Int. 2015;39:690-5 pubmed publisher
    b>Smad ubiquitination regulatory factor 2 (Smurf2) consists of multiple WW domains which can interact with Smad7 molecule and inhibit signaling of transforming growth factor-beta (TGF-β) cytokine...
  51. Siegert A, Serra Peinado C, Gutiérrez Martínez E, Rodriguez Pascual F, Fabregat I, Egea G. Altered TGF-? endocytic trafficking contributes to the increased signaling in Marfan syndrome. Biochim Biophys Acta Mol Basis Dis. 2018;1864:554-562 pubmed publisher
    ..We examined molecular components involved in clathrin- (SARA, SMAD2) and caveolin-1- (SMAD7, SMURF2) dependent endocytosis...
  52. 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. ..
  53. Zepp J, Wu L, Qian W, Ouyang W, Aronica M, Erzurum S, et al. TRAF4-SMURF2-mediated DAZAP2 degradation is critical for IL-25 signaling and allergic airway inflammation. J Immunol. 2015;194:2826-37 pubmed publisher
    ..Mechanistically, TRAF4 recruited the E3-ligase SMURF2, to degrade the IL-25R-inhibitory molecule DAZAP2...
  54. Zhou F, Xie F, Jin K, Zhang Z, Clerici M, Gao R, et al. USP4 inhibits SMAD4 monoubiquitination and promotes activin and BMP signaling. EMBO J. 2017;36:1623-1639 pubmed publisher
    ..This modification was triggered by the recruitment of the E3 ligase, SMURF2, to SMAD4 following ligand-induced regulatory (R)-SMAD-SMAD4 complex formation...
  55. Emanuelli A, Borroni A, Apel Sarid L, Shah P, Ayyathan D, Koganti P, et al. Smurf2-Mediated Stabilization of DNA Topoisomerase IIα Controls Genomic Integrity. Cancer Res. 2017;77:4217-4227 pubmed publisher
    ..Here, we identify the E3 ubiquitin ligase Smurf2 as a physiologic regulator of Topo IIα levels...
  56. Iyengar P, Jaynes P, Rodón L, Lama D, Law K, Lim Y, et al. USP15 regulates SMURF2 kinetics through C-lobe mediated deubiquitination. Sci Rep. 2015;5:14733 pubmed publisher
    ..limit TGF-β responses, TGF-β signaling is regulated through a negative feedback loop whereby the E3 ligase SMURF2 targets the TGF-β receptor (TβR) complex for ubiquitin-mediated degradation...
  57. Li Y, Werner H, Püschel A. Rheb and mTOR regulate neuronal polarity through Rap1B. J Biol Chem. 2008;283:33784-92 pubmed publisher
    ..The ubiquitin E3 ligase Smurf2 mediates the restriction of Rap1B by initiating its degradation...
  58. Xiao L, Peng X, Liu F, Tang C, Hu C, Xu X, et al. AKT regulation of mesothelial-to-mesenchymal transition in peritoneal dialysis is modulated by Smurf2 and deubiquitinating enzyme USP4. BMC Cell Biol. 2015;16:7 pubmed publisher
    ..Upregulation of pAkt paralleled with the increased expression of Smad ubiquitination regulatory factor 2 (Smurf2), Vimentin and fibronectin (FN), and decreased expression of mothers against ..
  59. Fleet A, Lee J, Tamachi A, Javeed I, Hamel P. Activities of the Cytoplasmic Domains of Patched-1 Modulate but Are Not Essential for the Regulation of Canonical Hedgehog Signaling. J Biol Chem. 2016;291:17557-68 pubmed publisher
    ..Hh pathway and responds to the addition of Hh ligand independent of its inability to bind other factors such as Smurf2. Additionally, deletion of the cytoplasmic middle loop domain generates a Ptch1 mutant that, despite binding to Hh ..
  60. Keszei A, Sicheri F. Mechanism of catalysis, E2 recognition, and autoinhibition for the IpaH family of bacterial E3 ubiquitin ligases. Proc Natl Acad Sci U S A. 2017;114:1311-1316 pubmed publisher
    ..This mode of autoinhibition, which is not shared by the HECT domain ligase Smurf2, leads to the unanticipated depletion of E2∼Ub and thus a concomitant dominant-negative effect on other E3s ..
  61. Sun Y, Zhou M, Fu D, Xu B, Fang T, Ma Y, et al. Ubiquitination of heat shock protein 27 is mediated by its interaction with Smad ubiquitination regulatory factor 2 in A549 cells. Exp Lung Res. 2011;37:568-73 pubmed publisher
    b>Smad ubiquitination regulatory factor 2 (Smurf2) is a crucial part of the ubiquitin-proteasome pathway (UPP) that regulates cellular signal transduction via ubiquitin-dependent degradation of some substrates and receptors...
  62. Verga Gérard A, Porcherot M, Meyniel Schicklin L, Andre P, Lotteau V, Perrin Cocon L. Hepatitis C virus/human interactome identifies SMURF2 and the viral protease as critical elements for the control of TGF-? signaling. FASEB J. 2013;27:4027-40 pubmed publisher
    ..We found that the viral protease NS3-4A interacted with SMURF2, a negative regulator of TGF-? signaling...
  63. Yu Y, Chou R, Shyu W, Hsieh S, Wu C, Chiang S, et al. Smurf2-mediated degradation of EZH2 enhances neuron differentiation and improves functional recovery after ischaemic stroke. EMBO Mol Med. 2013;5:531-47 pubmed publisher
    ..Here, we identify Smurf2 as the E3 ubiquitin ligase responsible for the polyubiquitination and proteasome-mediated degradation of EZH2, ..
  64. He K, Yan X, Li N, Dang S, Xu L, Zhao B, et al. Internalization of the TGF-β type I receptor into caveolin-1 and EEA1 double-positive early endosomes. Cell Res. 2015;25:738-52 pubmed publisher
    ..We further showed that the caveolin-1-positive early endosomes are positive for Smad3/SARA, Rab11 and Smad7/Smurf2, and may act as a multifunctional device for TGF-β signaling and TGF-β receptor recycling and degradation...
  65. Kaneki H, Guo R, Chen D, Yao Z, Schwarz E, Zhang Y, et al. Tumor necrosis factor promotes Runx2 degradation through up-regulation of Smurf1 and Smurf2 in osteoblasts. J Biol Chem. 2006;281:4326-33 pubmed
    ..protein levels are regulated by proteasomal degradation, mediated by the E3 ubiquitin ligases, Smurf1 and Smurf2. We hypothesized that TNF inhibits osteoblast function through Smurf-mediated Runx2 degradation...
  66. Lee J, Cheng R, Honig L, Feitosa M, Kammerer C, Kang M, et al. Genome wide association and linkage analyses identified three loci-4q25, 17q23.2, and 10q11.21-associated with variation in leukocyte telomere length: the Long Life Family Study. Front Genet. 2013;4:310 pubmed publisher
    ..with SNPs, and our gene-wise association analysis identified multiple genes, including DCAF7, POLG2, CEP95, and SMURF2 at 17q23.2; and RASGEF1A, HNRNPF, ANF487, CSTF2T, and PRKG1 at 10q11.21...
  67. Shu J, Liu C, Wei R, Xie P, He S, Zhang L. Nedd8 targets ubiquitin ligase Smurf2 for neddylation and promote its degradation. Biochem Biophys Res Commun. 2016;474:51-56 pubmed publisher
    ..HECT-type ubiquitin ligase Smad ubiquitination regulatory factor 2 (Smurf2) has been demonstrated functions as a tumor suppressor...
  68. Wang Z, Gao Y, Zhang C, Hu H, Guo D, Xu Y, et al. Quinolinate Phosphoribosyltransferase is an Antiviral Host Factor Against Hepatitis C Virus Infection. Sci Rep. 2017;7:5876 pubmed publisher
    ..Mechanistic studies indicated that HCV NS3/4A promoted proteasomal degradation of QPRT through Smurf2, an E3 ubiquitin-protein ligase, in Huh7.5.1 cells...
  69. Jäckl M, Stollmaier C, Strohäker T, Hyz K, Maspero E, Polo S, et al. ?-Sheet Augmentation Is a Conserved Mechanism of Priming HECT E3 Ligases for Ubiquitin Ligation. J Mol Biol. 2018;430:3218-3233 pubmed publisher
    ..insights into the catalytic mechanism of the HECT-type ligase Huwe1 and compare it to the unrelated, K63-specific Smurf2 E3, a member of the Nedd4 family...
  70. Ohashi N, Yamamoto T, Uchida C, Togawa A, Fukasawa H, Fujigaki Y, et al. Transcriptional induction of Smurf2 ubiquitin ligase by TGF-beta. FEBS Lett. 2005;579:2557-63 pubmed
    b>Smad ubiquitination regulatory factor 2 (Smurf2), a ubiquitin ligase for Smads, plays critical roles in the regulation of transforming growth factor-beta (TGF-beta)-Smad signaling via ubiquitin-dependent degradation of Smad2 and Smad7...
  71. Li X, Diao Z, Ding J, Liu R, Wang L, Huang W, et al. The downregulation of SnoN expression in human renal proximal tubule epithelial cells under high-glucose conditions is mediated by an increase in Smurf2 expression through TGF-β1 signaling. Int J Mol Med. 2016;37:415-22 pubmed publisher
    ..In the present study, we demonstrated that the upregulation of Smad ubiquitination regulatory factor-2 (Smurf2), through TGF-β1/Smad signaling, contributes to the downregulation of SnoN under high-glucose conditions in ..
  72. Moore F, Osmundson E, Koblinski J, Pugacheva E, Golemis E, Ray D, et al. The WW-HECT protein Smurf2 interacts with the Docking Protein NEDD9/HEF1 for Aurora A activation. Cell Div. 2010;5:22 pubmed publisher
    ..Here we demonstrate that the HECT-WW protein Smurf2 physically associates with NEDD9 and is required for the stability of NEDD9 protein...
  73. Hou X, Jin Z, Jiang F, Zhu J, Li Z. Expression of Smad7 and Smad ubiquitin regulatory factor 2 in a rat model of chronic pancreatitis. J Dig Dis. 2015;16:408-15 pubmed publisher
    To quantify the expressions of Smad7 and Smad ubiquitin regulatory factor 2 (Smurf2) in the pancreas in rats with chronic pancreatitis (CP)...
  74. Huang P, Chung I, Lin Y, Lin T, Chen W, Lin K. The Long Non-Coding RNA MIR503HG Enhances Proliferation of Human ALK-Negative Anaplastic Large-Cell Lymphoma. Int J Mol Sci. 2018;19: pubmed publisher
    ..proliferation was mediated by the induction of microRNA-503 (miR-503) and suppression of Smurf2, resulting in stabilization of the tumor growth factor-? receptor (TGFBR) and enhanced tumor cell growth...
  75. Li D, Ohshiro K, Reddy S, Pakala S, Lee M, Zhang Y, et al. E3 ubiquitin ligase COP1 regulates the stability and functions of MTA1. Proc Natl Acad Sci U S A. 2009;106:17493-8 pubmed publisher
    ..These findings provide novel insights into the regulation of MTA1 protein and reveal a novel function of MTA1 in DNA damage response. ..
  76. Zhang L, Luga V, Armitage S, Musiol M, Won A, Yip C, et al. A lateral signalling pathway coordinates shape volatility during cell migration. Nat Commun. 2016;7:11714 pubmed publisher
    ..Pk1-mediated lateral signalling confines protrusive activity and is regulated by Smurf2, an E3 ubiquitin ligase in the PCP pathway...
  77. Beheshti A, Vanderburg C, McDonald J, Ramkumar C, Kadungure T, Zhang H, et al. A Circulating microRNA Signature Predicts Age-Based Development of Lymphoma. PLoS ONE. 2017;12:e0170521 pubmed publisher
    ..We harnessed a novel murine model of spontaneous DLBCL initiation (Smurf2-deficient) at two age groups: 3 and 15 months old...
  78. Xu Z, Diao Z, Liu R, Liu W. Molecular mechanism of smurf2 in regulating the expression of SnoN in diabetic nephropathy. Mol Med Rep. 2017;15:2560-2566 pubmed publisher
    ..cultured to clarify the effect of small mothers against decapentaplegic (Smad) ubiquitination regulatory factor 2 (smurf2) on SnoN in a low glucose environment in vitro...
  79. 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
    ..protein, but not Smad7, and mediated by recruitment of the Smad ubiquitin regulator factor proteins, Smurf1 and Smurf2, which have E3-ubiquitin ligase activity...
  80. Cai Y, Zhou C, Fu D, Shen X. Overexpression of Smad ubiquitin regulatory factor 2 suppresses transforming growth factor-? mediated liver fibrosis. J Dig Dis. 2012;13:327-34 pubmed publisher
    To determine the function of Smad ubiquitin regulatory factor 2 (Smurf2) on the development of liver fibrosis and cirrhosis...
  81. Li C, Hancock M, Sehgal P, Zhou S, Reinhardt D, Philip A. Soluble CD109 binds TGF-β and antagonizes TGF-β signalling and responses. Biochem J. 2016;473:537-47 pubmed publisher
    ..and responses and demonstrated that membrane-anchored CD109 promotes TGF-β receptor degradation via a SMAD7/Smurf2-mediated mechanism...
  82. Li Y, Xie P, Lu L, Wang J, Diao L, Liu Z, et al. An integrated bioinformatics platform for investigating the human E3 ubiquitin ligase-substrate interaction network. Nat Commun. 2017;8:347 pubmed publisher
    ..Here, the authors take an in silico naïve Bayesian classifier approach to integrate multiple lines of evidence for E3-substrate prediction, enabling prediction of the proteome-wide human E3 ligase interaction network. ..
  83. Bouin A, Kyumurkov A, Régent Kloeckner M, Ribba A, Faurobert E, Fournier H, et al. ICAP-1 monoubiquitylation coordinates matrix density and rigidity sensing for cell migration through ROCK2-MRCK? balance. J Cell Sci. 2017;130:626-636 pubmed publisher
    ..ICAP-1 monoubiquitylation serves as a molecular switch to coordinate extracellular matrix density and rigidity sensing thus acting as a crucial modulator of cell migration and mechanosensing. ..
  84. Wu Q, Huang J. Ectopic expression of Smurf2 and acceleration of age-related intervertebral disc degeneration in a mouse model. J Neurosurg Spine. 2017;27:116-126 pubmed publisher
    ..The goal of this study was to characterize how ectopic expression of Smurf2 driven by the collagen Type II alpha 1 ( Col2a1) promoter alters disc cell phenotype and associated cellular ..
  85. Zhao C, Xu Z, Wang Z, Suo C, Tao J, Han Z, et al. Role of tumor necrosis factor-? in epithelial-to-mesenchymal transition in transplanted kidney cells in recipients with chronic allograft dysfunction. Gene. 2018;642:483-490 pubmed publisher
    ..Cell motility and migration were assessed using wound healing and transwell assays. Expression of Smurf2 and TNF-?-signaling pathway-related proteins in HK-2 cells treated with TNF-? was detected by western blotting...
  86. Carpentier I, Coornaert B, Beyaert R. Smurf2 is a TRAF2 binding protein that triggers TNF-R2 ubiquitination and TNF-R2-induced JNK activation. Biochem Biophys Res Commun. 2008;374:752-7 pubmed publisher
    ..This resulted in the identification of the E3 ubiquitin ligase Smurf2 as a TRAF2 binding protein...
  87. Lu K, Wang B, Chi W, Chang Chien J, Yang J, Lee H, et al. Ovatodiolide Inhibits Breast Cancer Stem/Progenitor Cells through SMURF2-Mediated Downregulation of Hsp27. Toxins (Basel). 2016;8: pubmed publisher
    ..4 (Oct4) and Nanog, as well as heat shock protein 27 (Hsp27), but upregulated SMAD ubiquitin regulatory factor 2 (SMURF2) in mammosphere cells derived from AS-B145 or BT-474...
  88. Popova A, Kzhyshkowska J, Nurgazieva D, Goerdt S, Gratchev A. Smurf2 regulates IL17RB by proteasomal degradation of its novel binding partner DAZAP2. Immunobiology. 2012;217:321-8 pubmed publisher
    ..Further we established that DAZAP2 interacts with Smurf2 an E3 ubiquitin ligase which induces proteasome-dependent degradation of the protein...
  89. 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
    ..Here we show that mice deficient in SMURF2 have severe osteoporosis in vivo...
  90. Wottrich S, Kaufhold S, Chrysos E, Zoras O, Baritaki S, Bonavida B. Inverse correlation between the metastasis suppressor RKIP and the metastasis inducer YY1: Contrasting roles in the regulation of chemo/immuno-resistance in cancer. Drug Resist Updat. 2017;30:28-38 pubmed publisher
    ..cross-talk pathways include the following loops: RKIP/NF-κB/Snail/YY1, p38/MAPK/RKIP/GSK3β/Snail/YY1, RKIP/Smurf2/YY1/Snail, RKIP/MAPK/Myc/Let-7/HMGA2/Snail/YY1, as well as RKIP/GPCR/STAT3/miR-34/YY1...
  91. Manikoth Ayyathan D, Ilic N, Gil Henn H, Blank M. Generation of SMURF2 knockout human cells using the CRISPR/Cas9 system. Anal Biochem. 2017;531:56-59 pubmed publisher
    The HECT domain E3 ubiquitin ligase SMURF2 regulates stability of several key protein targets involved in tumorigenesis, cell proliferation, migration, differentiation, and senescence...
  92. Huang Y, Yang Y, Gao R, Yang X, Yan X, Wang C, et al. RLIM interacts with Smurf2 and promotes TGF-? induced U2OS cell migration. Biochem Biophys Res Commun. 2011;414:181-5 pubmed publisher
    ..Here we found a novel E3 ubiquitin ligase RLIM which can directly bind to Smurf2, enhancing TGF-? responsiveness in osteosarcoma U2OS cells...