Suppressor of cytokine signaling 1 is a protein that in humans is encoded by the SOCS1gene.[1][2]SOCS1orthologs[3] have been identified in several mammals for which complete genome data are available.
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, IL3erythropoietin (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:
↑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. PMID9266833.
↑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. PMID11297560.
↑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. PMID10585430.
↑Rui L, Yuan M, Frantz D, Shoelson S, White MF (November 2002). "SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2". The Journal of Biological Chemistry. 277 (44): 42394–8. doi:10.1074/jbc.C200444200. PMID12228220.
↑Dif F, Saunier E, Demeneix B, Kelly PA, Edery M (December 2001). "Cytokine-inducible SH2-containing protein suppresses PRL signaling by binding the PRL receptor". Endocrinology. 142 (12): 5286–93. doi:10.1210/endo.142.12.8549. PMID11713228.
↑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. doi:10.1038/43213. PMID9202126.
↑Pezet A, Favre H, Kelly PA, Edery M (August 1999). "Inhibition and restoration of prolactin signal transduction by suppressors of cytokine signaling". The Journal of Biological Chemistry. 274 (35): 24497–502. doi:10.1074/jbc.274.35.24497. PMID10455112.
↑Masuhara M, Sakamoto H, Matsumoto A, Suzuki R, Yasukawa H, Mitsui K, Wakioka T, Tanimura S, Sasaki A, Misawa H, Yokouchi M, Ohtsubo M, Yoshimura A (October 1997). "Cloning and characterization of novel CIS family genes". Biochemical and Biophysical Research Communications. 239 (2): 439–46. doi:10.1006/bbrc.1997.7484. PMID9344848.
↑Ohya K, Kajigaya S, Yamashita Y, Miyazato A, Hatake K, Miura Y, Ikeda U, Shimada K, Ozawa K, Mano H (October 1997). "SOCS-1/JAB/SSI-1 can bind to and suppress Tec protein-tyrosine kinase". The Journal of Biological Chemistry. 272 (43): 27178–82. doi:10.1074/jbc.272.43.27178. PMID9341160.
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. PMID11835308.
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. PMID12076535.
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. doi:10.1038/43206. PMID9202125.
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. doi:10.1038/43213. PMID9202126.
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. PMID9727029.
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. PMID10490100.
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. PMID10512686.
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. PMID10517496.
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. PMID10585430.
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. PMID11133764.
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. PMID11297560.
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. PMID11342531.