Gene Symbol: SOCS3
Description: suppressor of cytokine signaling 3
Alias: ATOD4, CIS3, Cish3, SOCS-3, SSI-3, SSI3, suppressor of cytokine signaling 3, STAT-induced STAT inhibitor 3, cytokine-inducible SH2 protein 3
Species: human
Products:     SOCS3

Top Publications

  1. Senn J, Klover P, Nowak I, Zimmers T, Koniaris L, Furlanetto R, et al. Suppressor of cytokine signaling-3 (SOCS-3), a potential mediator of interleukin-6-dependent insulin resistance in hepatocytes. J Biol Chem. 2003;278:13740-6 pubmed
    ..These data suggest that induction of SOCS-3 in liver may be an important mechanism of IL-6-mediated insulin resistance. ..
  2. Miao T, Wu D, Zhang Y, Bo X, Xiao F, Zhang X, et al. SOCS3 suppresses AP-1 transcriptional activity in neuroblastoma cells through inhibition of c-Jun N-terminal kinase. Mol Cell Neurosci. 2008;37:367-75 pubmed
    ..Overexpression of SOCS3 (suppressor of cytokine signaling) inhibited and mutant SOCS3 (with an inactivating point mutation in amino acid ..
  3. Elliott J, Suessmuth Y, Scott L, Nahlik K, McMullin M, Constantinescu S, et al. SOCS3 tyrosine phosphorylation as a potential bio-marker for myeloproliferative neoplasms associated with mutant JAK2 kinases. Haematologica. 2009;94:576-80 pubmed publisher
    JAK2 V617F, identified in the majority of patients with myeloproliferative neoplasms, tyrosine phosphorylates SOCS3 and escapes its inhibition...
  4. Sasi W, Jiang W, Sharma A, Mokbel K. Higher expression levels of SOCS 1,3,4,7 are associated with earlier tumour stage and better clinical outcome in human breast cancer. BMC Cancer. 2010;10:178 pubmed publisher
    ..Higher mRNA expression levels of SOCS1, 3, 4 and 7 are significantly associated with earlier tumour stage and better clinical outcome in human breast cancer. ..
  5. Seki Y, Inoue H, Nagata N, Hayashi K, Fukuyama S, Matsumoto K, et al. SOCS-3 regulates onset and maintenance of T(H)2-mediated allergic responses. Nat Med. 2003;9:1047-54 pubmed
    ..In contrast, dominant-negative mutant SOCS-3 transgenic mice, as well as mice with a heterozygous deletion of Socs3, had decreased T(H)2 development...
  6. Persico M, Capasso M, Persico E, Svelto M, Russo R, Spano D, et al. Suppressor of cytokine signaling 3 (SOCS3) expression and hepatitis C virus-related chronic hepatitis: Insulin resistance and response to antiviral therapy. Hepatology. 2007;46:1009-15 pubmed
    ..Overexpression of the suppressor of cytokine signaling 3 (SOCS3) gene in liver tissue is associated with a poorer treatment outcome in patients with chronic ..
  7. He Y, Zhang W, Zhang R, Zhang H, Min W. SOCS1 inhibits tumor necrosis factor-induced activation of ASK1-JNK inflammatory signaling by mediating ASK1 degradation. J Biol Chem. 2006;281:5559-66 pubmed
    ..We concluded that SOCS1 functions as a negative regulator in TNF-induced inflammation in EC, in part, by inducing ASK1 degradation. ..
  8. Barclay J, Anderson S, Waters M, Curlewis J. SOCS3 as a tumor suppressor in breast cancer cells, and its regulation by PRL. Int J Cancer. 2009;124:1756-66 pubmed publisher
    b>Suppressor of cytokine signaling 3 (SOCS3), as a key regulator of cytokine signaling, has the potential to modulate numerous cellular processes...
  9. He B, You L, Uematsu K, Matsangou M, Xu Z, He M, et al. Cloning and characterization of a functional promoter of the human SOCS-3 gene. Biochem Biophys Res Commun. 2003;301:386-91 pubmed
    ..Cloning of the human SOCS-3 promoter should help uncover mechanisms of regulation of the JAK-STAT pathway in human cancer. ..

More Information


  1. Ram P, Waxman D. SOCS/CIS protein inhibition of growth hormone-stimulated STAT5 signaling by multiple mechanisms. J Biol Chem. 1999;274:35553-61 pubmed
  2. Niemand C, Nimmesgern A, Haan S, Fischer P, Schaper F, Rossaint R, et al. Activation of STAT3 by IL-6 and IL-10 in primary human macrophages is differentially modulated by suppressor of cytokine signaling 3. J Immunol. 2003;170:3263-72 pubmed
    ..Although LPS induces the feedback inhibitor suppressor of cytokine signaling 3 (SOCS3) in macrophages, inhibition of IL-6 signal transduction by LPS occurs rapidly and does not ..
  3. Funaoka Y, Sakamoto N, Suda G, Itsui Y, Nakagawa M, Kakinuma S, et al. Analysis of interferon signaling by infectious hepatitis C virus clones with substitutions of core amino acids 70 and 91. J Virol. 2011;85:5986-94 pubmed publisher
    ..The expression level of an interferon signal attenuator, SOCS3, was significantly higher for the R70Q, R70H, and L91M mutants than for the wild type...
  4. Yokota S, Yokosawa N, Okabayashi T, Suzutani T, Miura S, Jimbow K, et al. Induction of suppressor of cytokine signaling-3 by herpes simplex virus type 1 contributes to inhibition of the interferon signaling pathway. J Virol. 2004;78:6282-6 pubmed
    ..In the present study, we showed that the suppressor of cytokine signaling-3 (SOCS3), a host negative regulator of the JAK/STAT pathway, is rapidly induced in FL cells after HSV-1 infection...
  5. Pothlichet J, Chignard M, Si Tahar M. Cutting edge: innate immune response triggered by influenza A virus is negatively regulated by SOCS1 and SOCS3 through a RIG-I/IFNAR1-dependent pathway. J Immunol. 2008;180:2034-8 pubmed
    ..Src homology 2-containing protein (CIS), are constitutively expressed in these cells and only SOCS1 and SOCS3 expressions are up-regulated upon IAV challenge...
  6. Niwa Y, Kanda H, Shikauchi Y, Saiura A, Matsubara K, Kitagawa T, et al. Methylation silencing of SOCS-3 promotes cell growth and migration by enhancing JAK/STAT and FAK signalings in human hepatocellular carcinoma. Oncogene. 2005;24:6406-17 pubmed
    ..Thus, loss of SOCS-3 by the associated DNA methylation confers cells advantage in growth and migration. ..
  7. Hashimoto K, Ishibashi K, Ishioka K, Zhao D, Sato M, Ohara S, et al. RSV replication is attenuated by counteracting expression of the suppressor of cytokine signaling (SOCS) molecules. Virology. 2009;391:162-70 pubmed publisher
    ..RSV infection up-regulated SOCS1, SOCS3, and CIS mRNA expression in HEp-2 cells...
  8. Schmitz J, Weissenbach M, Haan S, Heinrich P, Schaper F. SOCS3 exerts its inhibitory function on interleukin-6 signal transduction through the SHP2 recruitment site of gp130. J Biol Chem. 2000;275:12848-56 pubmed the signal transduction pathway of interleukin-6 and demonstrate that the tyrosine phosphatase SHP2 and SOCS3 do not act independently but are functionally linked...
  9. Sakai I, Takeuchi K, Yamauchi H, Narumi H, Fujita S. Constitutive expression of SOCS3 confers resistance to IFN-alpha in chronic myelogenous leukemia cells. Blood. 2002;100:2926-31 pubmed
    ..This study reports on the constitutive expression of SOCS3 in most chronic myelogenous leukemia (CML) cell lines, which are resistant to treatment with interferon alpha (IFN-..
  10. Sasaki A, Yasukawa H, Suzuki A, Kamizono S, Syoda T, Kinjyo I, et al. Cytokine-inducible SH2 protein-3 (CIS3/SOCS3) inhibits Janus tyrosine kinase by binding through the N-terminal kinase inhibitory region as well as SH2 domain. Genes Cells. 1999;4:339-51 pubmed
    ..We also identified another JAK-binding protein, CIS3 (cytokine-inducible SH2-protein 3, or SOCS3) that inhibits signalling of various cytokines...
  11. Sutherland K, Lindeman G, Choong D, Wittlin S, Brentzell L, Phillips W, et al. Differential hypermethylation of SOCS genes in ovarian and breast carcinomas. Oncogene. 2004;23:7726-33 pubmed
    ..b>SOCS3 was not hypermethylated in either cancer type...
  12. Isomoto H, Mott J, Kobayashi S, Werneburg N, Bronk S, Haan S, et al. Sustained IL-6/STAT-3 signaling in cholangiocarcinoma cells due to SOCS-3 epigenetic silencing. Gastroenterology. 2007;132:384-96 pubmed
    ..Because suppressor of cytokine signaling 3 (SOCS) controls the IL-6/STAT-3 signaling pathway by a classic feedback loop, the aims of this study ..
  13. Fernandez Mercado M, Cebrian V, Euba B, García Granero M, Calasanz M, Novo F, et al. Methylation status of SOCS1 and SOCS3 in BCR-ABL negative and JAK2V617F negative chronic myeloproliferative neoplasms. Leuk Res. 2008;32:1638-40 pubmed publisher
  14. Martini M, Pallini R, Luongo G, Cenci T, Lucantoni C, Larocca L. Prognostic relevance of SOCS3 hypermethylation in patients with glioblastoma multiforme. Int J Cancer. 2008;123:2955-60 pubmed publisher
    ..Moreover, methylation of SOCS3 promoter significantly associated with an unfavorable clinical outcome (p < 0.0002)...
  15. Koeberlein B, zur Hausen A, Bektas N, Zentgraf H, Chin R, Nguyen L, et al. Hepatitis B virus overexpresses suppressor of cytokine signaling-3 (SOCS3) thereby contributing to severity of inflammation in the liver. Virus Res. 2010;148:51-9 pubmed publisher
    ..Recent reports have shown that SOCS3 activation interferes with viral protein expression and treatment response and thereby plays a major role in ..
  16. Liu Y, Dong W, Chen L, Xiang R, Xiao H, De G, et al. BCL10 mediates lipopolysaccharide/toll-like receptor-4 signaling through interaction with Pellino2. J Biol Chem. 2004;279:37436-44 pubmed
    ..In addition, we found that BCL10 was targeted by SOCS3 for negative regulation in LPS signaling...
  17. Ying M, Li D, Yang L, Wang M, Wang N, Chen Y, et al. Loss of SOCS3 expression is associated with an increased risk of recurrent disease in breast carcinoma. J Cancer Res Clin Oncol. 2010;136:1617-26 pubmed publisher
    Constitutive activation of JAK/STAT pathway is observed in various solid tumors and hematological malignancies. SOCS3 acts as a key negative regulator of JAK/STAT pathway and represents one of the candidate tumor suppressor genes...
  18. Bode J, Ludwig S, Freitas C, Schaper F, Ruhl M, Melmed S, et al. The MKK6/p38 mitogen-activated protein kinase pathway is capable of inducing SOCS3 gene expression and inhibits IL-6-induced transcription. Biol Chem. 2001;382:1447-53 pubmed
    ..Pretreatment of cells with the p38MAPK-specific inhibitor SB202190 downregulates the induction of SOCS3-mRNA expression by IL-6...
  19. Yang S, Yeh Y, Wang S, Hung S, Chen W, Huang C, et al. SOCS-3 is associated with vascular invasion and overall survival in hepatocellular carcinoma. Pathology. 2008;40:558-63 pubmed publisher
    ..Constitutive and altered SOCS-3 expression may have potential roles in a subset of HCC patients. ..
  20. Neuwirt H, Puhr M, Cavarretta I, Mitterberger M, Hobisch A, Culig Z. Suppressor of cytokine signalling-3 is up-regulated by androgen in prostate cancer cell lines and inhibits androgen-mediated proliferation and secretion. Endocr Relat Cancer. 2007;14:1007-19 pubmed
    ..Taken together with previous findings showing androgen receptor activation by IL-6, our results imply that androgen and cytokine signalling pathways interact at multiple levels in prostate cancer. ..
  21. Rui L, Yuan M, Frantz D, Shoelson S, White M. SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2. J Biol Chem. 2002;277:42394-8 pubmed
    ..Inflammation induces the expression of SOCS proteins. We show that SOCS1 or SOCS3 targeted IRS1 and IRS2, two critical signaling molecules for insulin action, for ubiquitin-mediated degradation...
  22. Evans M, Yu C, Lohani A, Mahdi R, Liu X, Trzeciak A, et al. Expression of SOCS1 and SOCS3 genes is differentially regulated in breast cancer cells in response to proinflammatory cytokine and growth factor signals. Oncogene. 2007;26:1941-8 pubmed breast, ovarian, squamous cell and hepatocellular carcinoma has led to speculation that silencing of SOCS1 and SOCS3 genes might promote oncogenic transformation of epithelial tissues...
  23. Huang W, Yang S, Wu C, Chen W, Huang Y, Su Y, et al. Expression of signal transducer and activator of transcription 3 and suppressor of cytokine signaling 3 in urothelial carcinoma. Kaohsiung J Med Sci. 2009;25:640-6 pubmed publisher
    ..expression of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) Tyr705 and suppressor of cytokine signaling 3 (SOCS3) in urothelial carcinoma (UC)...
  24. Bruun C, Heding P, Rønn S, Frobøse H, Rhodes C, Mandrup Poulsen T, et al. Suppressor of cytokine signalling-3 inhibits Tumor necrosis factor-alpha induced apoptosis and signalling in beta cells. Mol Cell Endocrinol. 2009;311:32-8 pubmed publisher
    ..The ability of SOCS-3 to regulate signalling induced by the three major pro-inflammatory cytokines involved in the pathogenesis of T1DM makes SOCS-3 an interesting therapeutic candidate for protection of the beta cell mass. ..
  25. Hebenstreit D, Luft P, Schmiedlechner A, Duschl A, Horejs Hoeck J. SOCS-1 and SOCS-3 inhibit IL-4 and IL-13 induced activation of Eotaxin-3/CCL26 gene expression in HEK293 cells. Mol Immunol. 2005;42:295-303 pubmed
    ..The insertion of amino acid exchanges into the kinase inhibitory regions of SOCS-1 and SOCS-3 demonstrated a requirement of these domains for a proper inhibitory function. ..
  26. Soriano S, Hernanz Falcón P, Rodríguez Frade J, De Ana A, Garzón R, Carvalho Pinto C, et al. Functional inactivation of CXC chemokine receptor 4-mediated responses through SOCS3 up-regulation. J Exp Med. 2002;196:311-21 pubmed
    ..We show that SOCS3 overexpression or up-regulation, stimulated by a cytokine such as growth hormone, impairs the response to CXCL12, ..
  27. Steinberg G, McAinch A, Chen M, O Brien P, Dixon J, Cameron Smith D, et al. The suppressor of cytokine signaling 3 inhibits leptin activation of AMP-kinase in cultured skeletal muscle of obese humans. J Clin Endocrinol Metab. 2006;91:3592-7 pubmed
    ..and recent studies have demonstrated that hypothalamic expression of the suppressors of cytokine signaling 3 (SOCS3) regulates leptin sensitivity in rodents...
  28. Pauli E, Schmolke M, Wolff T, Viemann D, Roth J, Bode J, et al. Influenza A virus inhibits type I IFN signaling via NF-kappaB-dependent induction of SOCS-3 expression. PLoS Pathog. 2008;4:e1000196 pubmed publisher
    ..The inhibitory effect is at least in part due to the induction of SOCS-3 gene expression, which results in an impaired antiviral response. ..
  29. Oguro T, Ishibashi K, Sugino T, Hashimoto K, Tomita S, Takahashi N, et al. Humanised antihuman IL-6R antibody with interferon inhibits renal cell carcinoma cell growth in vitro and in vivo through suppressed SOCS3 expression. Eur J Cancer. 2013;49:1715-24 pubmed publisher
    ..Suppressor of cytokine signalling-3 (SOCS3) is rapidly up-regulated by IL-6 and a negative regulator of cytokine signalling...
  30. Babon J, Kershaw N, Murphy J, Varghese L, Laktyushin A, Young S, et al. Suppression of cytokine signaling by SOCS3: characterization of the mode of inhibition and the basis of its specificity. Immunity. 2012;36:239-50 pubmed publisher
    Janus kinases (JAKs) are key effectors in controlling immune responses and maintaining hematopoiesis. SOCS3 (suppressor of cytokine signaling-3) is a major regulator of JAK signaling and here we investigate the molecular basis of its ..
  31. Lindemann C, Hackmann O, Delic S, Schmidt N, Reifenberger G, Riemenschneider M. SOCS3 promoter methylation is mutually exclusive to EGFR amplification in gliomas and promotes glioma cell invasion through STAT3 and FAK activation. Acta Neuropathol. 2011;122:241-51 pubmed publisher
    The suppressor of cytokine signaling 3 (SOCS3) gene is one of eight structurally related genes of the SOCS family and has been suggested to function as a tumor suppressor by inhibition of the JAK/STAT signaling pathway...
  32. Fukushima A, Kajiya H, Izumi T, Shigeyama C, Okabe K, Anan H. Pro-inflammatory cytokines induce suppressor of cytokine signaling-3 in human periodontal ligament cells. J Endod. 2010;36:1004-8 pubmed publisher
    ..The SOCS-3 induction suggests playing an important role in negative feedback, suppressing serious destruction of periodontal tissue in apical periodontitis through a chemokine-dependent mechanism. ..
  33. Jamshidi Y, Snieder H, Wang X, Spector T, Carter N, O Dell S. Common polymorphisms in SOCS3 are not associated with body weight, insulin sensitivity or lipid profile in normal female twins. Diabetologia. 2006;49:306-10 pubmed
    ..between three single-nucleotide polymorphisms (SNPs) representative of common linkage disequilibrium clusters in SOCS3 (rs4969169, rs12953258 and rs8064821) and obesity measures, insulin sensitivity measures and serum lipids in the ..
  34. Yasukawa H, Sasaki A, Yoshimura A. Negative regulation of cytokine signaling pathways. Annu Rev Immunol. 2000;18:143-64 pubmed
    ..appear to be induced after stimulation with several different cytokines, and at least three of them (CIS1, CIS3/SOCS3, and JAB/SOCS1) negatively regulate cytokine signal transduction by various means: CIS1 inhibits STAT5 activation ..
  35. Bjorbak C, Lavery H, Bates S, Olson R, Davis S, Flier J, et al. SOCS3 mediates feedback inhibition of the leptin receptor via Tyr985. J Biol Chem. 2000;275:40649-57 pubmed
    ..suggest that Tyr(985) may mediate feedback inhibition of LRb signaling by an LRb-induced LRb inhibitor, such as SOCS3. Indeed, SOCS3 binds specifically to phosphorylated Tyr(985) of LRb, and SOCS3 fails to inhibit transcription by ..
  36. Ortiz Muñoz G, Martin Ventura J, Hernandez Vargas P, Mallavia B, Lopez Parra V, Lopez Franco O, et al. Suppressors of cytokine signaling modulate JAK/STAT-mediated cell responses during atherosclerosis. Arterioscler Thromb Vasc Biol. 2009;29:525-31 pubmed publisher
    ..Immunohistochemistry in human plaques revealed a high expression of SOCS1 and SOCS3 by vascular smooth muscle cells (VSMCs) and macrophages in the inflammatory region of the shoulders, when compared ..
  37. Ye L, Wang X, Metzger D, Riedel E, Montaner L, Ho W. Upregulation of SOCS-3 and PIAS-3 impairs IL-12-mediated interferon-gamma response in CD56 T cells in HCV-infected heroin users. PLoS ONE. 2010;5:e9602 pubmed publisher
    ..These findings provide compelling in vivo evidence that heroin use or heroin use plus HCV infection impairs CD56(+) T cell-mediated innate immune function, which may account for HCV infection and persistence in liver. ..
  38. Li Y, Deuring J, Peppelenbosch M, Kuipers E, de Haar C, van der Woude C. IL-6-induced DNMT1 activity mediates SOCS3 promoter hypermethylation in ulcerative colitis-related colorectal cancer. Carcinogenesis. 2012;33:1889-96 pubmed publisher
    ..IL)-6 signaling towards signal transducer and activator of transcription 3 activation through the loss of SOCS3 expression, unleashing the full carcinogenic potential of this transcription factor...
  39. Gylvin T, Nolsøe R, Hansen T, Nielsen E, Bergholdt R, Karlsen A, et al. Mutation analysis of suppressor of cytokine signalling 3, a candidate gene in Type 1 diabetes and insulin sensitivity. Diabetologia. 2004;47:1273-1277 pubmed publisher
    ..b>SOCS3 could therefore be a candidate gene in the development of Type 1 and Type 2 diabetes mellitus...
  40. Holter K, Wermter A, Scherag A, Siegfried W, Goldschmidt H, Hebebrand J, et al. Analysis of sequence variations in the suppressor of cytokine signaling (SOCS)-3 gene in extremely obese children and adolescents. BMC Med Genet. 2007;8:21 pubmed
    ..We investigated association of variations in the coding sequence and promoter region of SOCS3 with extreme obesity in German children and adolescents...
  41. Attia F, Hassan A, El Maraghy N, Ibrahium G. Clinical significance of suppressor of cytokines signalling-3 mRNA expression from patients with non-Hodgkin lymphoma under chemotherapy. Cancer Biomark. 2011;11:41-7 pubmed publisher
    ..SOCS-3 mRNA expression in peripheral blood from NHL patients might be used to monitor response during treatment. ..
  42. Wiejak J, Dunlop J, Gao S, Borland G, Yarwood S. Extracellular signal-regulated kinase mitogen-activated protein kinase-dependent SOCS-3 gene induction requires c-Jun, signal transducer and activator of transcription 3, and specificity protein 3 transcription factors. Mol Pharmacol. 2012;81:657-68 pubmed publisher
    ..Together these results describe novel, ERK-dependent regulation of transcriptional activity that requires codependent activation of multiple transcription factors within the same region of the SOCS-3 gene promoter. ..
  43. Tokumaru S, Sayama K, Yamasaki K, Shirakata Y, Hanakawa Y, Yahata Y, et al. SOCS3/CIS3 negative regulation of STAT3 in HGF-induced keratinocyte migration. Biochem Biophys Res Commun. 2005;327:100-5 pubmed
    ..Next, we studied the mechanisms that regulate STAT3 phosphorylation. HGF enhanced the expression of SOCS3/CIS3 by sixfold within 1h, but had minimum effect on SOCS1/JAB expression...
  44. Zhou H, Miki R, Eeva M, Fike F, Seligson D, Yang L, et al. Reciprocal regulation of SOCS 1 and SOCS3 enhances resistance to ionizing radiation in glioblastoma multiforme. Clin Cancer Res. 2007;13:2344-53 pubmed
    The expression of suppressors of cytokine signaling 1 (SOCS1) and SOCS3 genes is dysregulated in several solid tumors, causing aberrant activation of cell growth and survival signaling pathways...
  45. Masuhara M, Sakamoto H, Matsumoto A, Suzuki R, Yasukawa H, Mitsui K, et al. Cloning and characterization of novel CIS family genes. Biochem Biophys Res Commun. 1997;239:439-46 pubmed
    ..Here we cloned three additional CIS family genes (CIS2, CIS3, and CIS4) on the basis of an expression sequence tag (EST) database search...
  46. Rigby R, Simmons J, Greenhalgh C, Alexander W, Lund P. Suppressor of cytokine signaling 3 (SOCS3) limits damage-induced crypt hyper-proliferation and inflammation-associated tumorigenesis in the colon. Oncogene. 2007;26:4833-41 pubmed
    ..We hypothesized that suppressor of cytokine signaling-3 (SOCS3) is such a factor...
  47. Matthews J, Almlöf T, Kietz S, Leers J, Gustafsson J. Estrogen receptor-alpha regulates SOCS-3 expression in human breast cancer cells. Biochem Biophys Res Commun. 2005;335:168-74 pubmed
    ..In summary, this study shows that ERalpha directly regulates human SOCS-3 promoter activity in human breast cancer cells, thus modulating cytokine activity. ..
  48. Ozaki A, Seki Y, Fukushima A, Kubo M. The control of allergic conjunctivitis by suppressor of cytokine signaling (SOCS)3 and SOCS5 in a murine model. J Immunol. 2005;175:5489-97 pubmed
    ..Furthermore, SOCS3 was highly expressed at the disease site, and T cell-specific expression of SOCS3 deteriorated clinical and ..
  49. Frobøse H, Rønn S, Heding P, Mendoza H, Cohen P, Mandrup Poulsen T, et al. Suppressor of cytokine Signaling-3 inhibits interleukin-1 signaling by targeting the TRAF-6/TAK1 complex. Mol Endocrinol. 2006;20:1587-96 pubmed
    ..These results indicate that SOCS-3 inhibits IL-1 signal transduction by inhibiting ubiquitination of TRAF6, thus preventing association and activation of TAK1. ..
  50. Stevenson N, McFarlane C, Ong S, Nahlik K, Kelvin A, Addley M, et al. Suppressor of cytokine signalling (SOCS) 1 and 3 enhance cell adhesion and inhibit migration towards the chemokine eotaxin/CCL11. FEBS Lett. 2010;584:4469-74 pubmed publisher
    ..Our novel findings suggest that SOCS1 and 3 may control chemotaxis and adhesion by significantly enhancing both FAK and RhoA activity, thus localizing immune cells to the site of allergic inflammation. ..
  51. Talbert M, Langefeld C, Ziegler J, Mychaleckyj J, Haffner S, Norris J, et al. Polymorphisms near SOCS3 are associated with obesity and glucose homeostasis traits in Hispanic Americans from the Insulin Resistance Atherosclerosis Family Study. Hum Genet. 2009;125:153-62 pubmed publisher
    The SOCS3 gene product participates in the feedback inhibition of a range of cytokine signals...
  52. Dey B, Furlanetto R, Nissley P. Suppressor of cytokine signaling (SOCS)-3 protein interacts with the insulin-like growth factor-I receptor. Biochem Biophys Res Commun. 2000;278:38-43 pubmed
    ..Unlike SOCS-2, hSOCS-3 was phosphorylated on tyrosines in response to IGF-I addition to 293 cells. We conclude that SOCS-3 binds to the IGFIR and may be a direct substrate for the receptor tyrosine kinase. ..
  53. Tokita T, Maesawa C, Kimura T, Kotani K, Takahashi K, Akasaka T, et al. Methylation status of the SOCS3 gene in human malignant melanomas. Int J Oncol. 2007;30:689-94 pubmed
    ..Aberrant methylation in the promoter region of the SOCS3 gene frequently occurs in several types of human malignancy, and its transcriptional silencing is associated with ..
  54. Sands W, Woolson H, Milne G, Rutherford C, Palmer T. Exchange protein activated by cyclic AMP (Epac)-mediated induction of suppressor of cytokine signaling 3 (SOCS-3) in vascular endothelial cells. Mol Cell Biol. 2006;26:6333-46 pubmed
    ..This was associated with the induction of suppressor of cytokine signaling 3 (SOCS-3), a bona fide inhibitor in vivo of gp130, the signal-transducing component of the IL-6 ..
  55. Weber A, Hengge U, Bardenheuer W, Tischoff I, Sommerer F, Markwarth A, et al. SOCS-3 is frequently methylated in head and neck squamous cell carcinoma and its precursor lesions and causes growth inhibition. Oncogene. 2005;24:6699-708 pubmed
    ..During its involvement in tumor growth, restoration of SOCS-3 may hold treatment potential for HNSCC. ..
  56. He B, You L, Uematsu K, Zang K, Xu Z, Lee A, et al. SOCS-3 is frequently silenced by hypermethylation and suppresses cell growth in human lung cancer. Proc Natl Acad Sci U S A. 2003;100:14133-8 pubmed
    ..The data also suggest that SOCS-3 therapy may be useful in the treatment of cancer. ..
  57. Yang X, Albrecht U, Zakowski V, Sobota R, Haussinger D, Heinrich P, et al. Dual function of interleukin-1beta for the regulation of interleukin-6-induced suppressor of cytokine signaling 3 expression. J Biol Chem. 2004;279:45279-89 pubmed
    ..Herein we analyzed IL-1beta-mediated regulation of IL-6-induced expression of the feedback inhibitor SOCS3. In hepatocytes IL-1beta alone does not induce SOCS3 expression, but it counteracts SOCS3-promoter activation in ..
  58. Kim K, Lin W, Tai A, Shao R, Weinberg E, De Sa Borges C, et al. Hepatic SOCS3 expression is strongly associated with non-response to therapy and race in HCV and HCV/HIV infection. J Hepatol. 2009;50:705-11 pubmed publisher
    ..We measured the expression of signal transducer and activator of transcription 1 (STAT1) and suppressor of cytokine signaling 3 (SOCS3) in pretreatment liver biopsies. Staining quantitation was compared to treatment outcomes...
  59. White G, Cotterill A, Addley M, Soilleux E, Greaves D. Suppressor of cytokine signalling protein SOCS3 expression is increased at sites of acute and chronic inflammation. J Mol Histol. 2011;42:137-51 pubmed publisher
    ..We used immunohistochemistry to identify cells and pathologies where SOCS3 expression might influence acute and chronic inflammatory responses in human tissues...
  60. Roberts A, Robb L, Rakar S, Hartley L, Cluse L, Nicola N, et al. Placental defects and embryonic lethality in mice lacking suppressor of cytokine signaling 3. Proc Natl Acad Sci U S A. 2001;98:9324-9 pubmed
    Mice lacking suppressor of cytokine signaling 3 (SOCS3) exhibited embryonic lethality with death occurring between days 11 and 13 of gestation...
  61. Rieusset J, Bouzakri K, Chevillotte E, Ricard N, Jacquet D, Bastard J, et al. Suppressor of cytokine signaling 3 expression and insulin resistance in skeletal muscle of obese and type 2 diabetic patients. Diabetes. 2004;53:2232-41 pubmed
    ..We investigated whether IL-6 could inhibit insulin signaling in human skeletal myotubes and whether suppressor of cytokine signaling 3 (SOCS-3) could be related to insulin resistance in vivo in humans...
  62. Yokota S, Yokosawa N, Okabayashi T, Suzutani T, Fujii N. Induction of suppressor of cytokine signaling-3 by herpes simplex virus type 1 confers efficient viral replication. Virology. 2005;338:173-81 pubmed
    ..that infection of herpes simplex virus type 1 (HSV-1) rapidly induced the suppressor of cytokine signaling-3 (SOCS3), a host negative regulator of the JAK/STAT pathway, in the amnion cell line FL...
  63. Ogata H, Kobayashi T, Chinen T, Takaki H, Sanada T, Minoda Y, et al. Deletion of the SOCS3 gene in liver parenchymal cells promotes hepatitis-induced hepatocarcinogenesis. Gastroenterology. 2006;131:179-93 pubmed
    A recent study has suggested that the methylation silencing of the suppressor of cytokine signaling-3 (SOCS3), a negative regulator of interleukin-6-related cytokines, could be involved in hepatocellular carcinoma (HCC)...
  64. Séron K, Corset L, Vasseur F, Boutin P, Gomez Ambrosi J, Salvador J, et al. Distinct impaired regulation of SOCS3 and long and short isoforms of the leptin receptor in visceral and subcutaneous fat of lean and obese women. Biochem Biophys Res Commun. 2006;348:1232-8 pubmed
    ..studies have illustrated the importance of the expression in adipose tissue of the leptin receptor (OB-R), and of SOCS3 an inhibitor of the leptin signaling pathway, in body weight regulation...
  65. Persico M, Capasso M, Russo R, Persico E, Croce L, Tiribelli C, et al. Elevated expression and polymorphisms of SOCS3 influence patient response to antiviral therapy in chronic hepatitis C. Gut. 2008;57:507-15 pubmed was performed, testing three single nucleotide polymorphisms (SNPs) of suppressor of cytokine signalling 3 (SOCS3) in 162 NR and 184 SVR subjects (SOCS3 -8464 A/C (rs12952093), -4874 A/G (rs4969170) and 1383 A/G, (rs4969168))...
  66. Stevenson N, Addley M, Ryan E, Boyd C, Carroll H, Paunovic V, et al. CCL11 blocks IL-4 and GM-CSF signaling in hematopoietic cells and hinders dendritic cell differentiation via suppressor of cytokine signaling expression. J Leukoc Biol. 2009;85:289-97 pubmed publisher
    ..In this study, we find that CCL11 induces suppressor of cytokine signaling (SOCS)1 and SOCS3 expression in murine macrophages, human monocytes, and dendritic cells (DCs)...
  67. Williams J, Palmer T. Unbiased identification of substrates for the Epac1-inducible E3 ubiquitin ligase component SOCS-3. Biochem Soc Trans. 2012;40:215-8 pubmed publisher
  68. Komyod W, Bohm M, Metze D, Heinrich P, Behrmann I. Constitutive suppressor of cytokine signaling 3 expression confers a growth advantage to a human melanoma cell line. Mol Cancer Res. 2007;5:271-81 pubmed
    ..We found a high-level constitutive expression of suppressors of cytokine signaling 3 (SOCS3) that did not further increase after cytokine treatment...
  69. Qin H, Holdbrooks A, Liu Y, Reynolds S, Yanagisawa L, Benveniste E. SOCS3 deficiency promotes M1 macrophage polarization and inflammation. J Immunol. 2012;189:3439-48 pubmed
    ..In this study, we have evaluated the influence of SOCS3 on macrophage polarization and function...
  70. Braunschweig A, Poehlmann T, Busch S, Schleussner E, Markert U. Signal transducer and activator of transcription 3 (STAT3) and Suppressor of Cytokine Signaling (SOCS3) balance controls cytotoxicity and IL-10 expression in decidual-like natural killer cell line NK-92. Am J Reprod Immunol. 2011;66:329-35 pubmed publisher
    ..the role of STAT3 for induction of cytotoxicity and to analyze the regulative role of its antagonist suppressor of cytokine signaling 3 (SOCS3). Furthermore, the influence of both factors on cytokine expression should be analyzed...
  71. van de Loo F, Veenbergen S, van den Brand B, Bennink M, Blaney Davidson E, Arntz O, et al. Enhanced suppressor of cytokine signaling 3 in arthritic cartilage dysregulates human chondrocyte function. Arthritis Rheum. 2012;64:3313-23 pubmed publisher
    To determine the expression of suppressor of cytokine signaling 3 (SOCS-3) in human articular chondrocytes and its functional consequences...
  72. Shao R, Zhang L, Peng L, Sun E, Chung W, Jang J, et al. Suppressor of cytokine signaling 3 suppresses hepatitis C virus replication in an mTOR-dependent manner. J Virol. 2010;84:6060-9 pubmed publisher
    We and others have observed that hepatic levels of suppressor of cytokine signaling 3 (SOCS3) are significantly higher in persons with chronic hepatitis C, particularly those who are nonresponders to interferon (IFN) treatment, than in ..
  73. Zou T, Ouyang L, Chen L, Dong W, Qiao H, Liu Y, et al. The role of microtubule-associated protein 1S in SOCS3 regulation of IL-6 signaling. FEBS Lett. 2008;582:4015-22 pubmed publisher
    ..In this report, microtubule-associated protein 1S (MAP1), a member of the MAP1 family, was identified as a novel SOCS3 interacting protein. MAP1S could bind with microtubules and actin, and decorated and stabilized microtubules...
  74. Fourouclas N, Li J, Gilby D, Campbell P, Beer P, Boyd E, et al. Methylation of the suppressor of cytokine signaling 3 gene (SOCS3) in myeloproliferative disorders. Haematologica. 2008;93:1635-44 pubmed publisher
    ..components of JAK/STAT signaling, such as the negative regulators suppressor of cytokine signaling 1 (SOCS1) and SOCS3, may contribute to the pathogenesis of both JAK2 V617F positive and negative myeloproliferative disorders...
  75. Barclay J, Anderson S, Waters M, Curlewis J. Characterization of the SOCS3 promoter response to prostaglandin E2 in T47D cells. Mol Endocrinol. 2007;21:2516-28 pubmed
    b>Suppressor of cytokine signaling 3 (SOCS3), a negative regulator of cytokine signaling, is expressed in breast cancer cells where it can modify sensitivity and responsiveness to cytokine signaling through the Janus kinase/signal ..
  76. Vlotides G, Sörensen A, Kopp F, Zitzmann K, Cengic N, Brand S, et al. SOCS-1 and SOCS-3 inhibit IFN-alpha-induced expression of the antiviral proteins 2,5-OAS and MxA. Biochem Biophys Res Commun. 2004;320:1007-14 pubmed
    ..These data suggest a potential role of SOCS proteins in IFN resistance during antiviral treatment. ..
  77. Zhang J, Farley A, Nicholson S, Willson T, Zugaro L, Simpson R, et al. The conserved SOCS box motif in suppressors of cytokine signaling binds to elongins B and C and may couple bound proteins to proteasomal degradation. Proc Natl Acad Sci U S A. 1999;96:2071-6 pubmed
    ..Analogous to the family of F-box-containing proteins, it appears that the SOCS proteins may act as adaptor molecules that target activated cell signaling proteins to the protein degradation pathway. ..
  78. Pierconti F, Martini M, Pinto F, Cenci T, Capodimonti S, Calarco A, et al. Epigenetic silencing of SOCS3 identifies a subset of prostate cancer with an aggressive behavior. Prostate. 2011;71:318-25 pubmed publisher
    ..In this way, molecular alterations of the suppressor of cytokine signaling 3 (SOCS3), one of the most important inhibitory molecule of inflammatory signal transduction ..
  79. Fischer Rosinsky A, Fisher E, Kovacs P, Bluher M, Mohlig M, Pfeiffer A, et al. Lack of association between the tagging SNP A+930-->G of SOCS3 and type 2 diabetes mellitus: meta-analysis of four independent study populations. PLoS ONE. 2008;3:e3852 pubmed publisher
    The suppressor of cytokine signalling 3 (SOCS3) provides a link between cytokine action and their negative consequences on insulin signalling. Thus SOCS3 is a potential candidate gene for type 2 diabetes (T2DM)...
  80. Le Y, Zhu B, Harley B, Park S, Kobayashi T, Manis J, et al. SOCS3 protein developmentally regulates the chemokine receptor CXCR4-FAK signaling pathway during B lymphopoiesis. Immunity. 2007;27:811-23 pubmed
    ..Here we demonstrate that suppressor of cytokine signaling 3 (SOCS3) regulated CXCL12-induced FAK phosphorylation through the ubiquitin-proteasome pathway...
  81. Brender C, Lovato P, Sommer V, Woetmann A, Mathiesen A, Geisler C, et al. Constitutive SOCS-3 expression protects T-cell lymphoma against growth inhibition by IFNalpha. Leukemia. 2005;19:209-13 pubmed
    ..In contrast, SOCS3 protects tumour cells against growth inhibition by IFNalpha...
  82. Yamamoto K, Yamaguchi M, Miyasaka N, Miura O. SOCS-3 inhibits IL-12-induced STAT4 activation by binding through its SH2 domain to the STAT4 docking site in the IL-12 receptor beta2 subunit. Biochem Biophys Res Commun. 2003;310:1188-93 pubmed
  83. Marine J, McKay C, Wang D, Topham D, Parganas E, Nakajima H, et al. SOCS3 is essential in the regulation of fetal liver erythropoiesis. Cell. 1999;98:617-27 pubmed
    b>SOCS3 (CIS3/JAB2) is an SH2-containing protein that binds to the activation loop of Janus kinases, inhibiting kinase activity, and thereby suppressing cytokine signaling...