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Suppressor of cytokine signaling 1
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<h2 id="function">Function</h2> <p>This gene encodes a member of the <a href="/facts/STAT_protein/E4L08eEa">STAT</a>-induced STAT inhibitor (SSI), also known as <a href="/facts/Suppressor_of_cytokine_signalling/r1Mlakfx">suppressor of cytokine signalling</a> (SOCS), family. SSI family members are cytokine-inducible negative regulators of <a href="/facts/Cytokine/SdWpWABH">cytokine</a> signaling. The expression of this gene can be induced by a subset of cytokines, including <a href="/facts/Interleukin_2/hH1DXu2W">IL2</a>, <a href="/facts/Interleukin_3/mXKTzRve">IL3</a>, <a href="/facts/Erythropoietin/jgYFo1R6">erythropoietin</a> (EPO), <a href="/facts/Granulocyte_macrophage_colony-stimulating_factor/U15M21QE">GM-CSF</a>, and <a href="/facts/Interferon-gamma/r51CXVph">interferon-gamma</a> (IFN-γ). The protein encoded by this gene functions downstream of cytokine receptors, and takes part in a <a href="/facts/Negative_feedback/G9byVgpN">negative feedback</a> loop to attenuate cytokine signaling. Knockout studies in mice suggested the role of this gene as a modulator of IFN-γ action, which is required for normal postnatal growth and survival.<a class="footnote-ref" id="fnref:4" href="#fn:4"><sup>4</sup></a> </p><p>Several recent viral studies have shown that viral genes, such as Tax gene product (Tax), encoded by HTLV-1, could hijack SOCS1 to inhibit host antiviral pathways, as a strategy to evade host immunity.<a class="footnote-ref" id="fnref:5" href="#fn:5"><sup>5</sup></a> </p> <h2 id="interactions">Interactions</h2> <p>The suppressor of cytokine signaling 1 has been shown to <a href="/facts/Protein-protein_interaction/etvm9Wmg">interact</a> with: </p> <ul><li><a href="/facts/Tax_gene_product/yqKGNHHz">Tax</a>,<a class="footnote-ref" id="fnref:6" href="#fn:6"><sup>6</sup></a></li> <li><a href="/facts/CD117/Lku3gt0m">CD117</a>,<a class="footnote-ref" id="fnref:7" href="#fn:7"><sup>7</sup></a></li> <li><a href="/facts/Colony_stimulating_factor_1_receptor/Av3kpU8F">Colony stimulating factor 1 receptor</a><a class="footnote-ref" id="fnref:8" href="#fn:8"><sup>8</sup></a></li> <li><a href="/facts/Growth_hormone_receptor/1G8TVrIu">Growth hormone receptor</a>,<a class="footnote-ref" id="fnref:9" href="#fn:9"><sup>9</sup></a></li> <li><a href="/facts/IRS2/xhutkDrW">IRS2</a>,<a class="footnote-ref" id="fnref:10" href="#fn:10"><sup>10</sup></a></li> <li><a href="/facts/Janus_kinase_2/yS2HKTU7">Janus kinase 2</a>,<a class="footnote-ref" id="fnref:11" href="#fn:11"><sup>11</sup></a><a class="footnote-ref" id="fnref:12" href="#fn:12"><sup>12</sup></a><a class="footnote-ref" id="fnref:13" href="#fn:13"><sup>13</sup></a><a class="footnote-ref" id="fnref:14" href="#fn:14"><sup>14</sup></a><a class="footnote-ref" id="fnref:15" href="#fn:15"><sup>15</sup></a><a class="footnote-ref" id="fnref:16" href="#fn:16"><sup>16</sup></a> and</li> <li><a href="/facts/TEC_(gene)/blh4xh6G">TEC</a>.<a class="footnote-ref" id="fnref:17" href="#fn:17"><sup>17</sup></a></li></ul> <h2 id="see-also">See also</h2> <ul><li><a href="/facts/SOCS/r1Mlakfx">SOCS</a></li> <li><a href="/facts/JAK-STAT_signaling_pathway/t31RBT3X">JAK-STAT signaling pathway</a></li></ul> <h2 id="further-reading">Further reading</h2> <ul><li>Krebs DL, Hilton DJ (2001). <a href="https://doi.org/10.1634%2Fstemcells.19-5-378">"SOCS proteins: negative regulators of cytokine signaling"</a>. <i>Stem Cells</i>. 19 (5): 378–87. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1634%2Fstemcells.19-5-378">10.1634/stemcells.19-5-378</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/11553846">11553846</a>.</li> <li>Wang J, Campbell IL (February 2002). <a href="https://doi.org/10.1002%2Fjnr.10145">"Cytokine signaling in the brain: putting a SOCS in it?"</a>. <i>Journal of Neuroscience Research</i>. 67 (4): 423–7. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1002%2Fjnr.10145">10.1002/jnr.10145</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/11835308">11835308</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:33269663">33269663</a>.</li> <li>Kile BT, Schulman BA, Alexander WS, Nicola NA, Martin HM, Hilton DJ (May 2002). "The SOCS box: a tale of destruction and degradation". <i>Trends in Biochemical Sciences</i>. 27 (5): 235–41. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2FS0968-0004%2802%2902085-6">10.1016/S0968-0004(02)02085-6</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/12076535">12076535</a>.</li> <li>Starr R, Willson TA, Viney EM, Murray LJ, Rayner JR, Jenkins BJ, Gonda TJ, Alexander WS, Metcalf D, Nicola NA, Hilton DJ (June 1997). <a href="https://doi.org/10.1038%2F43206">"A family of cytokine-inducible inhibitors of signalling"</a>. <i>Nature</i>. 387 (6636): 917–21. <a href="/facts/Bibcode_(identifier)/9HtdQSGB">Bibcode</a>:<a href="https://ui.adsabs.harvard.edu/abs/1997Natur.387..917S">1997Natur.387..917S</a>. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1038%2F43206">10.1038/43206</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/9202125">9202125</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:4325620">4325620</a>.</li> <li>Endo TA, Masuhara M, Yokouchi M, Suzuki R, Sakamoto H, Mitsui K, Matsumoto A, Tanimura S, Ohtsubo M, Misawa H, Miyazaki T, Leonor N, Taniguchi T, Fujita T, Kanakura Y, Komiya S, Yoshimura A (June 1997). <a href="https://doi.org/10.1038%2F43213">"A new protein containing an SH2 domain that inhibits JAK kinases"</a>. <i>Nature</i>. 387 (6636): 921–4. <a href="/facts/Bibcode_(identifier)/9HtdQSGB">Bibcode</a>:<a href="https://ui.adsabs.harvard.edu/abs/1997Natur.387..921E">1997Natur.387..921E</a>. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1038%2F43213">10.1038/43213</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/9202126">9202126</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:4347361">4347361</a>.</li> <li>Dey BR, Spence SL, Nissley P, Furlanetto RW (September 1998). <a href="https://doi.org/10.1074%2Fjbc.273.37.24095">"Interaction of human suppressor of cytokine signaling (SOCS)-2 with the insulin-like growth factor-I receptor"</a>. <i>The Journal of Biological Chemistry</i>. 273 (37): 24095–101. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1074%2Fjbc.273.37.24095">10.1074/jbc.273.37.24095</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/9727029">9727029</a>.</li> <li>De Sepulveda P, Okkenhaug K, Rose JL, Hawley RG, Dubreuil P, Rottapel R (February 1999). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1171183">"Socs1 binds to multiple signalling proteins and suppresses steel factor-dependent proliferation"</a>. <i>The EMBO Journal</i>. 18 (4): 904–15. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1093%2Femboj%2F18.4.904">10.1093/emboj/18.4.904</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1171183">1171183</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/10022833">10022833</a>.</li> <li>Zhang JG, Farley A, Nicholson SE, Willson TA, Zugaro LM, Simpson RJ, Moritz RL, Cary D, Richardson R, Hausmann G, Kile BT, Kile BJ, Kent SB, Alexander WS, Metcalf D, Hilton DJ, Nicola NA, Baca M (March 1999). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC26738">"The conserved SOCS box motif in suppressors of cytokine signaling binds to elongins B and C and may couple bound proteins to proteasomal degradation"</a>. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. 96 (5): 2071–6. <a href="/facts/Bibcode_(identifier)/9HtdQSGB">Bibcode</a>:<a href="https://ui.adsabs.harvard.edu/abs/1999PNAS...96.2071Z">1999PNAS...96.2071Z</a>. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1073%2Fpnas.96.5.2071">10.1073/pnas.96.5.2071</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC26738">26738</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/10051596">10051596</a>.</li> <li>Yasukawa H, Misawa H, Sakamoto H, Masuhara M, Sasaki A, Wakioka T, Ohtsuka S, Imaizumi T, Matsuda T, Ihle JN, Yoshimura A (March 1999). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1171221">"The JAK-binding protein JAB inhibits Janus tyrosine kinase activity through binding in the activation loop"</a>. <i>The EMBO Journal</i>. 18 (5): 1309–20. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1093%2Femboj%2F18.5.1309">10.1093/emboj/18.5.1309</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1171221">1171221</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/10064597">10064597</a>.</li> <li>Marine JC, Topham DJ, McKay C, Wang D, Parganas E, Stravopodis D, Yoshimura A, Ihle JN (September 1999). <a href="https://doi.org/10.1016%2FS0092-8674%2800%2980048-3">"SOCS1 deficiency causes a lymphocyte-dependent perinatal lethality"</a>. <i>Cell</i>. 98 (5): 609–16. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2FS0092-8674%2800%2980048-3">10.1016/S0092-8674(00)80048-3</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/10490100">10490100</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:14654250">14654250</a>.</li> <li>Yandava CN, Pillari A, Drazen JM (October 1999). "Radiation hybrid and cytogenetic mapping of SOCS1 and SOCS2 to chromosomes 16p13 and 12q, respectively". <i>Genomics</i>. 61 (1): 108–11. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1006%2Fgeno.1999.5937">10.1006/geno.1999.5937</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/10512686">10512686</a>.</li> <li>Okabe S, Tauchi T, Morita H, Ohashi H, Yoshimura A, Ohyashiki K (October 1999). <a href="https://doi.org/10.1016%2FS0301-472X%2899%2900094-6">"Thrombopoietin induces an SH2-containing protein, CIS1, which binds to Mpl: involvement of the ubiquitin proteosome pathway"</a>. <i>Experimental Hematology</i>. 27 (10): 1542–7. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2FS0301-472X%2899%2900094-6">10.1016/S0301-472X(99)00094-6</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/10517496">10517496</a>.</li> <li>Ram PA, Waxman DJ (December 1999). <a href="https://doi.org/10.1074%2Fjbc.274.50.35553">"SOCS/CIS protein inhibition of growth hormone-stimulated STAT5 signaling by multiple mechanisms"</a>. <i>The Journal of Biological Chemistry</i>. 274 (50): 35553–61. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1074%2Fjbc.274.50.35553">10.1074/jbc.274.50.35553</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/10585430">10585430</a>.</li> <li>Sporri B, Kovanen PE, Sasaki A, Yoshimura A, Leonard WJ (January 2001). <a href="https://doi.org/10.1182%2Fblood.V97.1.221">"JAB/SOCS1/SSI-1 is an interleukin-2-induced inhibitor of IL-2 signaling"</a>. <i>Blood</i>. 97 (1): 221–6. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1182%2Fblood.V97.1.221">10.1182/blood.V97.1.221</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/11133764">11133764</a>.</li> <li>Kawazoe Y, Naka T, Fujimoto M, Kohzaki H, Morita Y, Narazaki M, Okumura K, Saitoh H, Nakagawa R, Uchiyama Y, Akira S, Kishimoto T (January 2001). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193341">"Signal transducer and activator of transcription (STAT)-induced STAT inhibitor 1 (SSI-1)/suppressor of cytokine signaling 1 (SOCS1) inhibits insulin signal transduction pathway through modulating insulin receptor substrate 1 (IRS-1) phosphorylation"</a>. <i>The Journal of Experimental Medicine</i>. 193 (2): 263–9. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1084%2Fjem.193.2.263">10.1084/jem.193.2.263</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193341">2193341</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/11208867">11208867</a>.</li> <li>Bourette RP, De Sepulveda P, Arnaud S, Dubreuil P, Rottapel R, Mouchiroud G (June 2001). <a href="https://doi.org/10.1074%2Fjbc.M101878200">"Suppressor of cytokine signaling 1 interacts with the macrophage colony-stimulating factor receptor and negatively regulates its proliferation signal"</a>. <i>The Journal of Biological Chemistry</i>. 276 (25): 22133–9. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1074%2Fjbc.M101878200">10.1074/jbc.M101878200</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/11297560">11297560</a>.</li> <li>Mooney RA, Senn J, Cameron S, Inamdar N, Boivin LM, Shang Y, Furlanetto RW (July 2001). <a href="https://doi.org/10.1074%2Fjbc.M010579200">"Suppressors of cytokine signaling-1 and -6 associate with and inhibit the insulin receptor. A potential mechanism for cytokine-mediated insulin resistance"</a>. <i>The Journal of Biological Chemistry</i>. 276 (28): 25889–93. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1074%2Fjbc.M010579200">10.1074/jbc.M010579200</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/11342531">11342531</a>.</li> <li>Bellezza I, Neuwirt H, Nemes C, Cavarretta IT, Puhr M, Steiner H, Minelli A, Bartsch G, Offner F, Hobisch A, Doppler W, Culig Z (December 2006). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1762483">"Suppressor of cytokine signaling-3 antagonizes cAMP effects on proliferation and apoptosis and is expressed in human prostate cancer"</a>. <i>The American Journal of Pathology</i>. 169 (6): 2199–208. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.2353%2Fajpath.2006.060171">10.2353/ajpath.2006.060171</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1762483">1762483</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/17148681">17148681</a>.</li> <li>Neuwirt H, Puhr M, Santer FR, Susani M, Doppler W, Marcias G, Rauch V, Brugger M, Hobisch A, Kenner L, Culig Z (May 2009). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2671279">"Suppressor of cytokine signaling (SOCS)-1 is expressed in human prostate cancer and exerts growth-inhibitory function through down-regulation of cyclins and cyclin-dependent kinases"</a>. <i>The American Journal of Pathology</i>. 174 (5): 1921–30. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.2353%2Fajpath.2009.080751">10.2353/ajpath.2009.080751</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2671279">2671279</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/19342366">19342366</a>.</li></ul> <p><i>This article incorporates text from the <a href="/facts/United_States_National_Library_of_Medicine/Hzty0MCX">United States National Library of Medicine</a>, which is in the <a href="/facts/Public_domain/YWKMDKw4">public domain</a>.</i> </p> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>Yoshimura A, Ohkubo T, Kiguchi T, Jenkins NA, Gilbert DJ, Copeland NG, Hara T, Miyajima A (June 1995). "A novel cytokine-inducible gene CIS encodes an SH2-containing protein that binds to tyrosine-phosphorylated interleukin 3 and erythropoietin receptors". The EMBO Journal. 14 (12): 2816–26. doi:10.1002/j.1460-2075.1995.tb07281.x. PMC 398400. PMID 7796808. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC398400" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC398400</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>Minamoto S, Ikegame K, Ueno K, Narazaki M, Naka T, Yamamoto H, Matsumoto T, Saito H, Hosoe S, Kishimoto T (August 1997). "Cloning and functional analysis of new members of STAT induced STAT inhibitor (SSI) family: SSI-2 and SSI-3". Biochemical and Biophysical Research Communications. 237 (1): 79–83. doi:10.1006/bbrc.1997.7080. PMID 9266833. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>"OrthoMaM phylogenetic marker: SOCS1 coding sequence". <a href="http://www.orthomam.univ-montp2.fr/orthomam/data/cds/detailMarkers/ENSG00000185338_SOCS1.xml" target="_blank">http://www.orthomam.univ-montp2.fr/orthomam/data/cds/detailMarkers/ENSG00000185338_SOCS1.xml</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>"Entrez Gene: SOCS1 suppressor of cytokine signaling 1". <a href="https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8651" target="_blank">https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8651</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>Charoenthongtrakul S, Zhou Q, Shembade N, Harhaj NS, Harhaj EW (July 2011). "Human T cell leukemia virus type 1 Tax inhibits innate antiviral signaling via NF-kappaB-dependent induction of SOCS1". Journal of Virology. 85 (14): 6955–62. doi:10.1128/JVI.00007-11. PMC 3126571. PMID 21593151. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3126571" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3126571</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>Charoenthongtrakul S, Zhou Q, Shembade N, Harhaj NS, Harhaj EW (July 2011). "Human T cell leukemia virus type 1 Tax inhibits innate antiviral signaling via NF-kappaB-dependent induction of SOCS1". Journal of Virology. 85 (14): 6955–62. doi:10.1128/JVI.00007-11. PMC 3126571. 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