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Function

This gene encodes a member of the STAT-induced STAT inhibitor (SSI), also known as suppressor of cytokine signalling (SOCS), family. SSI family members are cytokine-inducible negative regulators of cytokine signaling. The expression of this gene can be induced by a subset of cytokines, including IL2, IL3, erythropoietin (EPO), GM-CSF, and interferon-gamma (IFN-γ). The protein encoded by this gene functions downstream of cytokine receptors, and takes part in a negative feedback 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.⁴

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.⁵

Interactions

The suppressor of cytokine signaling 1 has been shown to interact with:

• Tax,⁶
• CD117,⁷
• Colony stimulating factor 1 receptor⁸
• Growth hormone receptor,⁹
• IRS2,¹⁰
• Janus kinase 2,^111213141516 and
• TEC.¹⁷

See also

• SOCS
• JAK-STAT signaling pathway

Further reading

• Krebs DL, Hilton DJ (2001). "SOCS proteins: negative regulators of cytokine signaling". Stem Cells. 19 (5): 378–87. doi:10.1634/stemcells.19-5-378. PMID 11553846.
• Wang J, Campbell IL (February 2002). "Cytokine signaling in the brain: putting a SOCS in it?". Journal of Neuroscience Research. 67 (4): 423–7. doi:10.1002/jnr.10145. PMID 11835308. S2CID 33269663.
• Kile BT, Schulman BA, Alexander WS, Nicola NA, Martin HM, Hilton DJ (May 2002). "The SOCS box: a tale of destruction and degradation". Trends in Biochemical Sciences. 27 (5): 235–41. doi:10.1016/S0968-0004(02)02085-6. PMID 12076535.
• 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 family of cytokine-inducible inhibitors of signalling". Nature. 387 (6636): 917–21. Bibcode:1997Natur.387..917S. doi:10.1038/43206. PMID 9202125. S2CID 4325620.
• 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 new protein containing an SH2 domain that inhibits JAK kinases". Nature. 387 (6636): 921–4. Bibcode:1997Natur.387..921E. doi:10.1038/43213. PMID 9202126. S2CID 4347361.
• Dey BR, Spence SL, Nissley P, Furlanetto RW (September 1998). "Interaction of human suppressor of cytokine signaling (SOCS)-2 with the insulin-like growth factor-I receptor". The Journal of Biological Chemistry. 273 (37): 24095–101. doi:10.1074/jbc.273.37.24095. PMID 9727029.
• De Sepulveda P, Okkenhaug K, Rose JL, Hawley RG, Dubreuil P, Rottapel R (February 1999). "Socs1 binds to multiple signalling proteins and suppresses steel factor-dependent proliferation". The EMBO Journal. 18 (4): 904–15. doi:10.1093/emboj/18.4.904. PMC 1171183. PMID 10022833.
• 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). "The conserved SOCS box motif in suppressors of cytokine signaling binds to elongins B and C and may couple bound proteins to proteasomal degradation". Proceedings of the National Academy of Sciences of the United States of America. 96 (5): 2071–6. Bibcode:1999PNAS...96.2071Z. doi:10.1073/pnas.96.5.2071. PMC 26738. PMID 10051596.
• Yasukawa H, Misawa H, Sakamoto H, Masuhara M, Sasaki A, Wakioka T, Ohtsuka S, Imaizumi T, Matsuda T, Ihle JN, Yoshimura A (March 1999). "The JAK-binding protein JAB inhibits Janus tyrosine kinase activity through binding in the activation loop". The EMBO Journal. 18 (5): 1309–20. doi:10.1093/emboj/18.5.1309. PMC 1171221. PMID 10064597.
• Marine JC, Topham DJ, McKay C, Wang D, Parganas E, Stravopodis D, Yoshimura A, Ihle JN (September 1999). "SOCS1 deficiency causes a lymphocyte-dependent perinatal lethality". Cell. 98 (5): 609–16. doi:10.1016/S0092-8674(00)80048-3. PMID 10490100. S2CID 14654250.
• Yandava CN, Pillari A, Drazen JM (October 1999). "Radiation hybrid and cytogenetic mapping of SOCS1 and SOCS2 to chromosomes 16p13 and 12q, respectively". Genomics. 61 (1): 108–11. doi:10.1006/geno.1999.5937. PMID 10512686.
• Okabe S, Tauchi T, Morita H, Ohashi H, Yoshimura A, Ohyashiki K (October 1999). "Thrombopoietin induces an SH2-containing protein, CIS1, which binds to Mpl: involvement of the ubiquitin proteosome pathway". Experimental Hematology. 27 (10): 1542–7. doi:10.1016/S0301-472X(99)00094-6. PMID 10517496.
• Ram PA, Waxman DJ (December 1999). "SOCS/CIS protein inhibition of growth hormone-stimulated STAT5 signaling by multiple mechanisms". The Journal of Biological Chemistry. 274 (50): 35553–61. doi:10.1074/jbc.274.50.35553. PMID 10585430.
• Sporri B, Kovanen PE, Sasaki A, Yoshimura A, Leonard WJ (January 2001). "JAB/SOCS1/SSI-1 is an interleukin-2-induced inhibitor of IL-2 signaling". Blood. 97 (1): 221–6. doi:10.1182/blood.V97.1.221. PMID 11133764.
• 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). "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". The Journal of Experimental Medicine. 193 (2): 263–9. doi:10.1084/jem.193.2.263. PMC 2193341. PMID 11208867.
• Bourette RP, De Sepulveda P, Arnaud S, Dubreuil P, Rottapel R, Mouchiroud G (June 2001). "Suppressor of cytokine signaling 1 interacts with the macrophage colony-stimulating factor receptor and negatively regulates its proliferation signal". The Journal of Biological Chemistry. 276 (25): 22133–9. doi:10.1074/jbc.M101878200. PMID 11297560.
• Mooney RA, Senn J, Cameron S, Inamdar N, Boivin LM, Shang Y, Furlanetto RW (July 2001). "Suppressors of cytokine signaling-1 and -6 associate with and inhibit the insulin receptor. A potential mechanism for cytokine-mediated insulin resistance". The Journal of Biological Chemistry. 276 (28): 25889–93. doi:10.1074/jbc.M010579200. PMID 11342531.
• 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). "Suppressor of cytokine signaling-3 antagonizes cAMP effects on proliferation and apoptosis and is expressed in human prostate cancer". The American Journal of Pathology. 169 (6): 2199–208. doi:10.2353/ajpath.2006.060171. PMC 1762483. PMID 17148681.
• Neuwirt H, Puhr M, Santer FR, Susani M, Doppler W, Marcias G, Rauch V, Brugger M, Hobisch A, Kenner L, Culig Z (May 2009). "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". The American Journal of Pathology. 174 (5): 1921–30. doi:10.2353/ajpath.2009.080751. PMC 2671279. PMID 19342366.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

References

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