suppressor of cytokine signaling 3 protein


Summary: A suppressor of cytokine signaling protein that consists of an N-terminal kinase-inhibitory region, a central SH2 DOMAIN, a characteristic C-terminal SOCS box (a 40-amino acid motif, which functions to recruit E3 UBIQUITIN-PROTEIN LIGASE COMPLEXES). SOCS3 inhibits cytokine signaling by binding to RECEPTOR PROTEIN-TYROSINE KINASES as well as CYTOKINE RECEPTOR GP130; ERYTHROPOIETIN RECEPTORS; INSULIN RECEPTOR; and the LEPTIN RECEPTOR. Its functions include suppression of ERYTHROPOIESIS in the fetal liver.

Top Publications

  1. Lv R, Zhao J, Lei M, Xiao D, Yu Y, Xie J. IL-33 Attenuates Sepsis by Inhibiting IL-17 Receptor Signaling through Upregulation of SOCS3. Cell Physiol Biochem. 2017;42:1961-1972 pubmed publisher
    ..Collectively, the results suggest that IL-33 plays a negative regulatory role in sepsis progression by inhibiting IL-17 pathway through activating SOCS3. This finding would inspire a new therapeutic strategy for treating sepsis. ..
  2. Sato Y, Koshizuka T, Ishibashi K, Hashimoto K, Ishioka K, Ikuta K, et al. Involvement of herpes simplex virus type 1 UL13 protein kinase in induction of SOCS genes, the negative regulators of cytokine signaling. Microbiol Immunol. 2017;61:159-167 pubmed publisher
    ..Accumulation of activated Sp1 was detectable in the nuclei of HSV-1-infected cells before induction of SOCS3. Taken together, these results suggest that HSV-1 has a potent mechanism for escaping from the IFN system. ..
  3. Hoan N, Van Tong H, Giang D, Cuong B, Toan N, Wedemeyer H, et al. SOCS3 genetic variants and promoter hypermethylation in patients with chronic hepatitis B. Oncotarget. 2017;8:17127-17139 pubmed publisher
    ..0023). In conclusion, SOCS3 promoter variants are associated with HBV susceptibility and SOCS3 hypermethylation stimulates HCC development. ..
  4. Du J, Nicolaes G, Kruijswijk D, Versloot M, van der Poll T, Van T Veer C. The structure function of the death domain of human IRAK-M. Cell Commun Signal. 2014;12:77 pubmed publisher
    ..IRAK-M employs alternate residues of its DD to inhibit the different inflammatory mediators induced by varying TLRs and cells. ..
  5. Choe J, Park K, Park S, Lee S, Kim S. Regulatory effect of calcineurin inhibitor, tacrolimus, on IL-6/sIL-6R-mediated RANKL expression through JAK2-STAT3-SOCS3 signaling pathway in fibroblast-like synoviocytes. Arthritis Res Ther. 2013;15:R26 pubmed publisher
    ..These data suggest that tacrolimus might affect the RANKL expression in IL-6 stimulated FLS through STAT3 suppression, together with up-regulation of SOCS3. ..
  6. Chu Q, Shen D, He L, Wang H, Liu C, Zhang W. Prognostic significance of SOCS3 and its biological function in colorectal cancer. Gene. 2017;627:114-122 pubmed publisher
    ..Reduced expression of SOCS3 promoted the growth and metastasis of colorectal cancer. Thus, targeting IL-6/STAT3/SOCS3 signaling pathway may become an important treatment strategy of colorectal cancer. ..
  7. Chaligne R, Tonetti C, Besancenot R, Marty C, Kiladjian J, Socie G, et al. SOCS3 inhibits TPO-stimulated, but not spontaneous, megakaryocytic growth in primary myelofibrosis. Leukemia. 2009;23:1186-90 pubmed publisher
  8. Chikuma S, Kanamori M, Mise Omata S, Yoshimura A. Suppressors of cytokine signaling: Potential immune checkpoint molecules for cancer immunotherapy. Cancer Sci. 2017;108:574-580 pubmed publisher
    ..This review summarizes recent progress on CIS, SOCS1, and SOCS3 in terms of their anti-tumor immunity and potential applications. ..
  9. Blumer T, Coto Llerena M, Duong F, Heim M. SOCS1 is an inducible negative regulator of interferon λ (IFN-λ)-induced gene expression in vivo. J Biol Chem. 2017;292:17928-17938 pubmed publisher
    ..We found that IFN-α signaling is transient and becomes refractory after hours, whereas IFN-λ provides a long-lasting IFN-stimulated gene induction. ..

More Information


  1. Feng X, Tang S, Jiang Y, Zhao W. ANTI-DIABETIC EFFECTS OF ZHUODUQING FORMULA, A CHINESE HERBAL DECOCTION, ON A RAT MODEL OF TYPE 2 DIABETES. Afr J Tradit Complement Altern Med. 2017;14:42-50 pubmed publisher
  2. El Saadany S, Ziada D, El Bassat H, Farrag W, El Serogy H, Eid M, et al. The role of hepatic expression of STAT1, SOCS3 and PIAS1 in the response of chronic hepatitis C patients to therapy. Can J Gastroenterol. 2013;27:e13-7 pubmed
    ..These could be used as biomarkers that are easily detected by Western blotting or immunostaining during standard histopathological liver biopsy analysis. ..
  3. Vegran F, Berger H, Ghiringhelli F, Apetoh L. Socs3 induction by PPAR? restrains cancer-promoting inflammation. Cell Cycle. 2013;12:2157-8 pubmed
  4. Qin Y, Wu L, Ouyang Y, Zhou P, Zhou H, Wang Y, et al. MiR-125a Is a critical modulator for neutrophil development. PLoS Genet. 2017;13:e1007027 pubmed publisher
    ..Overall, our study revealed a new microRNA regulating granulocyte development and supported a model in which miR-125a acted as a fine-tuner of granulopoiesis...
  5. Ahmed Q, Manzoor S, Tariq M, Khalid M, Ashraf W, Parvaiz F, et al. Hepatitis C virus infection in vitro triggers endoplasmic reticulum stress and downregulates insulin receptor substrates 1 and 2 through upregulation of cytokine signaling suppressor 3. Acta Virol. 2014;58:238-44 pubmed
    ..Altogether these findings indicate that the HCV infection induces ER stress and IR in Huh-7 cells in vitro. ..
  6. Dayoub R, Buerger L, Ibrahim S, Melter M, Weiss T. Augmenter of liver regeneration (ALR) exhibits a dual signaling impact on hepatic acute-phase response. Exp Mol Pathol. 2017;102:428-433 pubmed publisher
    ..This study shows a dual signaling of ALR and suggests that ALR is pivotal for the regulation of APR, a crucial event in liver injury and regeneration. ..
  7. Lundtoft C, Afum Adjei Awuah A, Rimpler J, Harling K, Nausch N, Kohns M, et al. Aberrant plasma IL-7 and soluble IL-7 receptor levels indicate impaired T-cell response to IL-7 in human tuberculosis. PLoS Pathog. 2017;13:e1006425 pubmed publisher
    ..These findings show similarities to pathognomonic features of impaired T-cell functions and immune failure described in AIDS patients. ..
  8. Pedroso J, de Mendonca P, Fortes M, Tomaz I, Pecorali V, Auricino T, et al. SOCS3 expression in SF1 cells regulates adrenal differentiation and exercise performance. J Endocrinol. 2017;235:207-222 pubmed publisher
    ..Therefore, cytokine signaling in SF1 cells exerts an important role to sustain training performance possibly by promoting the necessary metabolic adjustments during exercise. ..
  9. Zhang Y, Ma C, Lawrence M, Break T, O Connell M, Lyons J, et al. PD-L1 up-regulation restrains Th17 cell differentiation in STAT3 loss- and STAT1 gain-of-function patients. J Exp Med. 2017;214:2523-2533 pubmed publisher
    ..PD-L1 may be a potential therapeutic target in several genetic diseases of immune deficiency affecting cytokine signaling. ..
  10. Kim E, Cheng Y, Bolton Gillespie E, Cai X, Ma C, Tarangelo A, et al. Rb family proteins enforce the homeostasis of quiescent hematopoietic stem cells by repressing Socs3 expression. J Exp Med. 2017;214:1901-1912 pubmed publisher
    ..Therefore, Rb proteins act as a central hub of quiescence and homeostasis by coordinating the regulation of both cell cycle and Jak2 signaling in HSCs. ..
  11. Cartoni R, Pekkurnaz G, Wang C, Schwarz T, He Z. A high mitochondrial transport rate characterizes CNS neurons with high axonal regeneration capacity. PLoS ONE. 2017;12:e0184672 pubmed publisher
    ..The results reported here suggest a pivotal role for this organelle during axonal regeneration. ..
  12. Wang X, Li T, Li M, Cao N, Han J. The Functional SOCS3 RS115785973 Variant Regulated by MiR-4308 Promotes Gastric Cancer Development in Chinese Population. Cell Physiol Biochem. 2016;38:1796-802 pubmed publisher
    ..Our findings have shown that the SNP rs115785973 in SOCS3 disrupting the regulatory role of miR-4308 in SOCS3 expression, rs115785973 in SOCS3 might act as a risk factor in the pathogenesis of GC. ..
  13. Wilbers R, van Raaij D, Westerhof L, Bakker J, Smant G, Schots A. Re-evaluation of IL-10 signaling reveals novel insights on the contribution of the intracellular domain of the IL-10R2 chain. PLoS ONE. 2017;12:e0186317 pubmed publisher
    ..This observation highlights a novel role for the intracellular domain of IL-10R2 in the molecular mechanisms of IL-10R activation. ..
  14. Li S, Chen S, Xu X, Sundstedt A, Paulsson K, Anderson P, et al. Cytokine-induced Src homology 2 protein (CIS) promotes T cell receptor-mediated proliferation and prolongs survival of activated T cells. J Exp Med. 2000;191:985-94 pubmed
    ..The functions of CIS, enhancing TCR signaling and inhibiting cytokine signaling, may be important in the regulation of immune response and homeostasis. ..
  15. Wonganan O, He Y, Shen X, Wongkrajang K, Suksamrarn A, Zhang G, et al. 6-Hydroxy-3-O-methyl-kaempferol 6-O-glucopyranoside potentiates the anti-proliferative effect of interferon ?/? by promoting activation of the JAK/STAT signaling by inhibiting SOCS3 in hepatocellular carcinoma cells. Toxicol Appl Pharmacol. 2017;336:31-39 pubmed publisher
    ..K6G warrants further investigation as a novel therapeutic method to enhance the efficacy of IFN-?/?. ..
  16. Xu Z, Ji J, Xu J, Li D, Shi G, Liu F, et al. MiR-30a increases MDSC differentiation and immunosuppressive function by targeting SOCS3 in mice with B-cell lymphoma. FEBS J. 2017;284:2410-2424 pubmed publisher
    ..These findings provide new insights into the molecular mechanisms underlying MDSC expansion and function during B cell lymphoma development. ..
  17. Singh S, Chouhan S, Mohammad N, Bhat M. Resistin causes G1 arrest in colon cancer cells through upregulation of SOCS3. FEBS Lett. 2017;591:1371-1382 pubmed publisher
    ..Interestingly, we observe that resistin-exposed cells survive 5-fluorouracil treatment because of a decrease in drug uptake due to the arrest of cells in G1 phase. ..
  18. Gui T, He B, Gan Q, Yang C. Enhanced SOCS3 in osteoarthiritis may limit both proliferation and inflammation. Biotech Histochem. 2017;92:107-114 pubmed publisher
    ..The anti-inflammation and growth inhibition effects exhibited by enhanced SOCS3 in OA appear to be related to its capacity to down-regulate expression levels of NF-?B and COX2. ..
  19. Hulse K, Chaung K, Seshadri S, Suh L, Norton J, Carter R, et al. Suppressor of cytokine signaling 3 expression is diminished in sinonasal tissues from patients with chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol. 2014;133:275-277.e1 pubmed publisher
  20. Vuolteenaho K, Koskinen A, Moilanen T, Moilanen E. Leptin levels are increased and its negative regulators, SOCS-3 and sOb-R are decreased in obese patients with osteoarthritis: a link between obesity and osteoarthritis. Ann Rheum Dis. 2012;71:1912-3 pubmed publisher
  21. Thangaratnarajah C, Dinger K, Vohlen C, Klaudt C, Nawabi J, López García E, et al. Novel role of NPY in neuroimmune interaction and lung growth after intrauterine growth restriction. Am J Physiol Lung Cell Mol Physiol. 2017;313:L491-L506 pubmed publisher
    ..These new insights in pulmonary neuroimmune interaction offer potential strategies to enable lung growth. ..
  22. Wang L, Xu J, Wu H, Zhang J, Tian Y. [Expression and role of TLR and SOCS mRNA in newborn infants]. Zhonghua Er Ke Za Zhi. 2006;44:621-2 pubmed