Genomes and Genes
suppressor of cytokine signaling proteins
Summary: A family of structurally related proteins that are induced by CYTOKINES and negatively regulate cytokine-mediated SIGNAL TRANSDUCTION PATHWAYS. SOCS proteins contain a central SH2 DOMAIN and a C-terminal region of homology known as the SOCS box.
- Zhang Y, Zhou B, Zhang F, Wu J, Hu Y, Liu Y, et al. Amyloid-? induces hepatic insulin resistance by activating JAK2/STAT3/SOCS-1 signaling pathway. Diabetes. 2012;61:1434-43 pubmed publisher..Our results demonstrate that A? induces hepatic insulin resistance by activating JAK2/STAT3/SOCS-1 signaling pathway and have implications toward resolving insulin resistance and T2DM. ..
- Palanivel R, Fullerton M, Galic S, Honeyman J, Hewitt K, Jorgensen S, et al. Reduced Socs3 expression in adipose tissue protects female mice against obesity-induced insulin resistance. Diabetologia. 2012;55:3083-93 pubmed publisher..These data demonstrate that inhibiting SOCS3 production in adipose tissue of female mice is effective for improving whole-body insulin sensitivity in obesity. ..
- Födermayr M, Zach O, Huber M, Machherndl Spandl S, Wölfl S, Bösmüller H, et al. The clinical impact of DNA methylation frequencies of JAK2 negative regulators in patients with essential thrombocythemia. Leuk Res. 2012;36:588-90 pubmed publisher..Taken together, regarding the genomic regions investigated our data indicate a minor role of methylation of JAK2 negative regulators for the clinical course of ET. ..
- Jorgensen S, O Neill H, Sylow L, Honeyman J, Hewitt K, Palanivel R, et al. Deletion of skeletal muscle SOCS3 prevents insulin resistance in obesity. Diabetes. 2013;62:56-64 pubmed publisher..Therapies aimed at inhibiting SOCS3 in skeletal muscle may be effective in reversing obesity-related glucose intolerance and insulin resistance. ..
- Oba T, Yasukawa H, Hoshijima M, Sasaki K, Futamata N, Fukui D, et al. Cardiac-specific deletion of SOCS-3 prevents development of left ventricular remodeling after acute myocardial infarction. J Am Coll Cardiol. 2012;59:838-52 pubmed publisher..Our data suggest that myocardial SOCS3 may be a key molecule in the development of LV remodeling after AMI. ..
- Fei X, Gu X, Fan S, Yang Z, Li F, Zhang C, et al. Crystal structure of Human ASB9-2 and substrate-recognition of CKB. Protein J. 2012;31:275-84 pubmed publisher..Analysis of truncation mutants demonstrated that the first six ankyrin repeats along with the N-terminal region of hASB9-2 contribute to the interaction with CKB. ..
- Qin H, Yeh W, De Sarno P, Holdbrooks A, Liu Y, Muldowney M, et al. Signal transducer and activator of transcription-3/suppressor of cytokine signaling-3 (STAT3/SOCS3) axis in myeloid cells regulates neuroinflammation. Proc Natl Acad Sci U S A. 2012;109:5004-9 pubmed publisher..These findings indicate that myeloid cell SOCS3 provides protection from EAE through deactivation of neuroinflammatory responses. ..
- Fingert J, Roos B, Solivan Timpe F, Miller K, Oetting T, Wang K, et al. Analysis of ASB10 variants in open angle glaucoma. Hum Mol Genet. 2012;21:4543-8 pubmed..These data suggest that non-synonymous mutations in ASB10 do not cause Mendelian forms of POAG. ..
- Yang Z, Hulver M, McMillan R, Cai L, Kershaw E, Yu L, et al. Regulation of insulin and leptin signaling by muscle suppressor of cytokine signaling 3 (SOCS3). PLoS ONE. 2012;7:e47493 pubmed publisher..These studies demonstrate that SOC3 within skeletal muscle is a critical regulator of leptin and insulin action and that increased SOCS may mediate insulin and leptin resistance in obesity. ..
- Yao R, Ma Y, Liang W, Li H, Ma Z, Yu X, et al. MicroRNA-155 modulates Treg and Th17 cells differentiation and Th17 cell function by targeting SOCS1. PLoS ONE. 2012;7:e46082 pubmed publisher..Therefore, we demonstrated that miR-155 enhanced Treg and Th17 cells differentiation and IL-17A production by targeting SOCS1. ..
- Ye J, Zheng R, Wang Q, Liao L, Ying Y, Lu H, et al. Downregulating SOCS3 with siRNA ameliorates insulin signaling and glucose metabolism in hepatocytes of IUGR rats with catch-up growth. Pediatr Res. 2012;72:550-9 pubmed publisher..Downregulating SOCS3 might improve insulin signaling transduction and ameliorate hepatic glucose metabolism in insulin-resistant CG-IUGR rats in vitro. ..
- Linossi E, Nicholson S. The SOCS box-adapting proteins for ubiquitination and proteasomal degradation. IUBMB Life. 2012;64:316-23 pubmed publisher..In general, the SOCS box-containing proteins are thought to act as substrate-recognition modules to mediate the polyubiquitination and subsequent degradation of substrate proteins by the 26S proteasome. ..
- 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..These findings collectively indicate that SOCS3 is involved in repressing the M1 proinflammatory phenotype, thereby deactivating inflammatory responses in macrophages. ..
- Zhuang G, Wu X, Jiang Z, Kasman I, Yao J, Guan Y, et al. Tumour-secreted miR-9 promotes endothelial cell migration and angiogenesis by activating the JAK-STAT pathway. EMBO J. 2012;31:3513-23 pubmed publisher..Collectively, these observations suggest that tumour-secreted miRNAs participate in intercellular communication and function as a novel pro-angiogenic mechanism. ..
- Feng Z, Chandrashekaran I, Low A, Speed T, Nicholson S, Norton R. The N-terminal domains of SOCS proteins: a conserved region in the disordered N-termini of SOCS4 and 5. Proteins. 2012;80:946-57 pubmed..The recombinant protein will be a valuable tool in identifying these partners and defining the structures of these complexes. ..
- Luckett Chastain L, Ihnat M, Mickle Kawar B, GALLUCCI R. SOCS3 modulates interleukin-6R signaling preference in dermal fibroblasts. J Interferon Cytokine Res. 2012;32:207-15 pubmed publisher..This study provides insight into the pleiotropic nature of IL-6 and the selective signaling mechanism elicited by the IL-6R system in dermal fibroblasts. It may further indicate a method for manipulation of IL-6R function. ..
- 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. ..
- Tomchuck S, Henkle S, Coffelt S, Betancourt A. Toll-like receptor 3 and suppressor of cytokine signaling proteins regulate CXCR4 and CXCR7 expression in bone marrow-derived human multipotent stromal cells. PLoS ONE. 2012;7:e39592 pubmed publisher..These results demonstrate that SOCS1 and SOCS3 each play a functionally distinct role in modulating TLR3, JAK/STAT, and CXCR4/CXCR7 signaling in hMSC and shed further light on the way hMSC respond to danger signals. ..
- Xu X, Wang Q, Deng B, Wang H, Dong Z, Qu X, et al. Monocyte chemoattractant protein-1 secreted by decidual stromal cells inhibits NK cells cytotoxicity by up-regulating expression of SOCS3. PLoS ONE. 2012;7:e41869 pubmed publisher..These findings suggest that the crosstalk between DSCs and NK cells may be crucial to maintain pregnancy homeostasis. ..
- 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. ..
- Collins E, Jager L, Dabelic R, Benitez P, Holdstein K, Lau K, et al. Inhibition of SOCS1-/- lethal autoinflammatory disease correlated to enhanced peripheral Foxp3+ regulatory T cell homeostasis. J Immunol. 2011;187:2666-76 pubmed publisher..In addition, these results strongly suggest that SOCS1 contributes to the stability of the Foxp3(+) Treg peripheral population under conditions of strong proinflammatory environments. ..
- Oberbach A, Schlichting N, Bluher M, Kovacs P, Till H, Stolzenburg J, et al. Palmitate induced IL-6 and MCP-1 expression in human bladder smooth muscle cells provides a link between diabetes and urinary tract infections. PLoS ONE. 2010;5:e10882 pubmed publisher..Induction of IL-6 in human bladder smooth muscle cells by fatty acids may represent a pathogenetic factor underlying the higher frequency and persistence of urinary tract infections in patients with metabolic diseases. ..
- Ahmed C, Dabelic R, Martin J, Jager L, Haider S, Johnson H. Enhancement of antiviral immunity by small molecule antagonist of suppressor of cytokine signaling. J Immunol. 2010;185:1103-13 pubmed publisher..The SOCS antagonist thus presents a novel and effective approach to enhancement of host defense against viruses. ..
- Hill G, Kuns R, Raffelt N, Don A, Olver S, Markey K, et al. SOCS3 regulates graft-versus-host disease. Blood. 2010;116:287-96 pubmed publisher..Thus, the delivery of small molecule SOCS3 mimetics may prove to be useful for the inhibition of both acute and chronic GVHD. ..
- 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. ..
- Whyte C, Bishop E, Rückerl D, Gaspar Pereira S, Barker R, Allen J, et al. Suppressor of cytokine signaling (SOCS)1 is a key determinant of differential macrophage activation and function. J Leukoc Biol. 2011;90:845-54 pubmed publisher..Together, our results uncover SOCS1, not only as a feedback inhibitor of inflammation but also as a critical molecular switch that tunes key signaling pathways to effectively program different sides of the macrophage balance. ..
- 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..0007) and with an unfavorable clinical outcome (P?=?0.0019). Our data suggest that SOCS3 hypermethylation may be involved in the pathogenesis of prostate cancer and could identify a tumor subset with an aggressive behavior. ..
- 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 other cytokines were expressed at very low concentration or not constantly affected. CONCLUSION? STAT3 and SOCS3 are involved in regulation of NK cell cytotoxicity and IL-10 expression...
- Jager L, Dabelic R, Waiboci L, Lau K, Haider M, Ahmed C, et al. The kinase inhibitory region of SOCS-1 is sufficient to inhibit T-helper 17 and other immune functions in experimental allergic encephalomyelitis. J Neuroimmunol. 2011;232:108-18 pubmed publisher..We have shown here that a SOCS-1 like effect can be obtained with a small functional region of the SOCS-1 protein that is easily produced. ..
- Pellegrini M, Calzascia T, Toe J, Preston S, Lin A, Elford A, et al. IL-7 engages multiple mechanisms to overcome chronic viral infection and limit organ pathology. Cell. 2011;144:601-13 pubmed publisher..The IL-7-mediated effects were dependent on endogenous IL-6. These attributes of IL-7 have profound implications for its use as a therapeutic in the treatment of chronic viral diseases...
- Ma X, Reynolds S, Baker B, Li X, Benveniste E, Qin H. IL-17 enhancement of the IL-6 signaling cascade in astrocytes. J Immunol. 2010;184:4898-906 pubmed publisher..These results indicate that astrocytes can serve as a target of Th17 cells and IL-17 in the CNS, and SOCS3 participates in IL-17 functions in the CNS as a negative feedback regulator. ..
- Ahmed S, Farquharson C. The effect of GH and IGF1 on linear growth and skeletal development and their modulation by SOCS proteins. J Endocrinol. 2010;206:249-59 pubmed publisher..Chronic inflammation is associated with altered growth and skeletal development, and it is possible that SOCS proteins may have an important role to play in mediating these effects. ..
- Sachithanandan N, Fam B, Fynch S, Dzamko N, Watt M, Wormald S, et al. Liver-specific suppressor of cytokine signaling-3 deletion in mice enhances hepatic insulin sensitivity and lipogenesis resulting in fatty liver and obesity. Hepatology. 2010;52:1632-42 pubmed publisher..Deletion of SOCS3 in the liver increases liver insulin sensitivity in mice fed a control diet but paradoxically promotes lipogenesis, leading to the development of nonalcoholic fatty liver disease, inflammation, and obesity. ..
- Wang P, Hou J, Lin L, Wang C, Liu X, Li D, et al. Inducible microRNA-155 feedback promotes type I IFN signaling in antiviral innate immunity by targeting suppressor of cytokine signaling 1. J Immunol. 2010;185:6226-33 pubmed publisher..Therefore, we demonstrate that inducible miR-155 feedback positively regulates host antiviral innate immune response by promoting type I IFN signaling via targeting SOCS1. ..
- 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..Expression of SOCS3 protein by leucocytes and other cell types in tissue sections could be a useful marker of cells undergoing acute or chronic stimulation by cytokines in vivo. ..
- Croker B, Kiu H, Pellegrini M, Toe J, Preston S, Metcalf D, et al. IL-6 promotes acute and chronic inflammatory disease in the absence of SOCS3. Immunol Cell Biol. 2012;90:124-9 pubmed publisher..We conclude that SOCS3 is required for survival during inflammatory responses and is a critical regulator of IL-6 in vivo. ..
- Hiwatashi K, Tamiya T, Hasegawa E, Fukaya T, Hashimoto M, Kakoi K, et al. Suppression of SOCS3 in macrophages prevents cancer metastasis by modifying macrophage phase and MCP2/CCL8 induction. Cancer Lett. 2011;308:172-80 pubmed publisher..Thus, the targeted inhibition of SOCS3 activity in macrophages may be therapeutic for the suppression of tumor metastasis. ..
- Ghanim H, Sia C, Upadhyay M, Upadhyay M, Korzeniewski K, Viswanathan P, et al. Orange juice neutralizes the proinflammatory effect of a high-fat, high-carbohydrate meal and prevents endotoxin increase and Toll-like receptor expression. Am J Clin Nutr. 2010;91:940-9 pubmed publisher..The intake of glucose or a high-fat, high-carbohydrate (HFHC) meal, but not orange juice, induces an increase in inflammation and oxidative stress in circulating mononuclear cells (MNCs) of normal-weight subjects...
- 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..In conclusion, HCV R70 and L91 core mutants were resistant to interferon in vitro, and the resistance may be induced by IL-6-induced upregulation of SOCS3. Those mechanisms may explain clinical interferon resistance of HCV core mutants. ..
- Tokuoka M, Miyoshi N, Hitora T, Mimori K, Tanaka F, Shibata K, et al. Clinical significance of ASB9 in human colorectal cancer. Int J Oncol. 2010;37:1105-11 pubmed..09; 95% confidence interval, 1.47-11.88; P=0.007). In an invasion assay, ASB9 siRNA-transfected cells showed significantly high invasiveness. The results of the present study suggest that ASB9 is a useful prognostic marker for CRC. ..
- de Souza J, Nogueira A, de Souza P, Cirelli J, Garlet G, Rossa C. Expression of suppressor of cytokine signaling 1 and 3 in ligature-induced periodontitis in rats. Arch Oral Biol. 2011;56:1120-8 pubmed publisher..This study suggests that SOCS1 and SOCS3 were directly correlated with regulatory mechanism of the inflammatory process responsible for the periodontal disease destruction. ..
- Moffatt C, Lamont R. Porphyromonas gingivalis induction of microRNA-203 expression controls suppressor of cytokine signaling 3 in gingival epithelial cells. Infect Immun. 2011;79:2632-7 pubmed publisher..This study shows that induction of miRNAs by P. gingivalis can modulate important host signaling responses. ..
- Hu G, Zhou R, Liu J, Gong A, Chen X. MicroRNA-98 and let-7 regulate expression of suppressor of cytokine signaling 4 in biliary epithelial cells in response to Cryptosporidium parvum infection. J Infect Dis. 2010;202:125-35 pubmed publisher..parvum. These data suggest that miRNAs play an important role in the coordinated regulation of CIS and SOCS expression in epithelial cells in response to C. parvum infection. ..
- Barrio S, Gallardo M, Albizua E, Jimenez A, Rapado I, Ayala R, et al. Epigenomic profiling in polycythaemia vera and essential thrombocythaemia shows low levels of aberrant DNA methylation. J Clin Pathol. 2011;64:1010-3 pubmed publisher..According to our results, an aberrant methylation pattern does not seem to play a crucial role in MPN pathogenesis; nor does it justify phenotypical differences between PV and ET. ..
- Whitmarsh R, Gray C, Gregg B, Christian D, May M, Murray P, et al. A critical role for SOCS3 in innate resistance to Toxoplasma gondii. Cell Host Microbe. 2011;10:224-36 pubmed publisher..Thus, SOCS3 has a critical role in suppressing IL-6 signals and promoting immune responses to control T. gondii infection. ..
- Li J, Chai B, Zhang W, Wu X, Zhang C, Fritze D, et al. Ankyrin repeat and SOCS box containing protein 4 (Asb-4) colocalizes with insulin receptor substrate 4 (IRS4) in the hypothalamic neurons and mediates IRS4 degradation. BMC Neurosci. 2011;12:95 pubmed publisher..These data demonstrated that Asb-4 co-localizes and interacts with IRS4 in hypothalamic neurons. The interaction of Asb-4 with IRS4 in cell lines mediates the degradation of IRS4 and decreases insulin signaling. ..
- Knosp C, Carroll H, Elliott J, Saunders S, Nel H, Amu S, et al. SOCS2 regulates T helper type 2 differentiation and the generation of type 2 allergic responses. J Exp Med. 2011;208:1523-31 pubmed publisher..Thus, we provide the first evidence that SOCS2 plays an important role in regulating Th2 cell expansion and development of the type 2 allergic responses. ..
- Jiang S, Zhang H, Lu M, He X, Li Y, Gu H, et al. MicroRNA-155 functions as an OncomiR in breast cancer by targeting the suppressor of cytokine signaling 1 gene. Cancer Res. 2010;70:3119-27 pubmed publisher..Taken together, our study reveals that miR-155 is an oncomiR in breast cancer and that miR-155 may be a potential target in breast cancer therapy. ..