Suppressor of cytokine signaling 1 explained

Suppressor of cytokine signaling 1 is a protein that in humans is encoded by the SOCS1 gene.^{[1] [2]} SOCS1 orthologs^[3] have been identified in several mammals for which complete genome data are available.

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,
• CD117,^[6]
• Colony stimulating factor 1 receptor^[7]
• Growth hormone receptor,^[8]
• IRS2,^[9]
• Janus kinase 2,^{[10] [11] [12] [13] [14] [15]} and
• TEC.^[16]

See also

• SOCS
• JAK-STAT signaling pathway

Further reading

• Krebs DL, Hilton DJ . SOCS proteins: negative regulators of cytokine signaling . Stem Cells . 19 . 5 . 378–87 . 2001 . 11553846 . 10.1634/stemcells.19-5-378 . free .
• Wang J, Campbell IL . Cytokine signaling in the brain: putting a SOCS in it? . Journal of Neuroscience Research . 67 . 4 . 423–7 . February 2002 . 11835308 . 10.1002/jnr.10145 . 33269663 . free .
• Kile BT, Schulman BA, Alexander WS, Nicola NA, Martin HM, Hilton DJ . The SOCS box: a tale of destruction and degradation . Trends in Biochemical Sciences . 27 . 5 . 235–41 . May 2002 . 12076535 . 10.1016/S0968-0004(02)02085-6 .
• Starr R, Willson TA, Viney EM, Murray LJ, Rayner JR, Jenkins BJ, Gonda TJ, Alexander WS, Metcalf D, Nicola NA, Hilton DJ . A family of cytokine-inducible inhibitors of signalling . Nature . 387 . 6636 . 917–21 . June 1997 . 9202125 . 10.1038/43206 . 1997Natur.387..917S . 4325620 . free .
• 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 . A new protein containing an SH2 domain that inhibits JAK kinases . Nature . 387 . 6636 . 921–4 . June 1997 . 9202126 . 10.1038/43213 . 1997Natur.387..921E . 4347361 . free .
• Dey BR, Spence SL, Nissley P, Furlanetto RW . 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 . September 1998 . 9727029 . 10.1074/jbc.273.37.24095 . free .
• De Sepulveda P, Okkenhaug K, Rose JL, Hawley RG, Dubreuil P, Rottapel R . Socs1 binds to multiple signalling proteins and suppresses steel factor-dependent proliferation . The EMBO Journal . 18 . 4 . 904–15 . February 1999 . 10022833 . 1171183 . 10.1093/emboj/18.4.904 .
• 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 . 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 . March 1999 . 10051596 . 26738 . 10.1073/pnas.96.5.2071 . 1999PNAS...96.2071Z . free .
• Yasukawa H, Misawa H, Sakamoto H, Masuhara M, Sasaki A, Wakioka T, Ohtsuka S, Imaizumi T, Matsuda T, Ihle JN, Yoshimura A . The JAK-binding protein JAB inhibits Janus tyrosine kinase activity through binding in the activation loop . The EMBO Journal . 18 . 5 . 1309–20 . March 1999 . 10064597 . 1171221 . 10.1093/emboj/18.5.1309 .
• Marine JC, Topham DJ, McKay C, Wang D, Parganas E, Stravopodis D, Yoshimura A, Ihle JN . SOCS1 deficiency causes a lymphocyte-dependent perinatal lethality . Cell . 98 . 5 . 609–16 . September 1999 . 10490100 . 10.1016/S0092-8674(00)80048-3 . 14654250 . free .
• Yandava CN, Pillari A, Drazen JM . Radiation hybrid and cytogenetic mapping of SOCS1 and SOCS2 to chromosomes 16p13 and 12q, respectively . Genomics . 61 . 1 . 108–11 . October 1999 . 10512686 . 10.1006/geno.1999.5937 .
• Okabe S, Tauchi T, Morita H, Ohashi H, Yoshimura A, Ohyashiki K . Thrombopoietin induces an SH2-containing protein, CIS1, which binds to Mpl: involvement of the ubiquitin proteosome pathway . Experimental Hematology . 27 . 10 . 1542–7 . October 1999 . 10517496 . 10.1016/S0301-472X(99)00094-6 . free .
• Ram PA, Waxman DJ . SOCS/CIS protein inhibition of growth hormone-stimulated STAT5 signaling by multiple mechanisms . The Journal of Biological Chemistry . 274 . 50 . 35553–61 . December 1999 . 10585430 . 10.1074/jbc.274.50.35553 . free .
• Sporri B, Kovanen PE, Sasaki A, Yoshimura A, Leonard WJ . JAB/SOCS1/SSI-1 is an interleukin-2-induced inhibitor of IL-2 signaling . Blood . 97 . 1 . 221–6 . January 2001 . 11133764 . 10.1182/blood.V97.1.221 . free .
• Kawazoe Y, Naka T, Fujimoto M, Kohzaki H, Morita Y, Narazaki M, Okumura K, Saitoh H, Nakagawa R, Uchiyama Y, Akira S, Kishimoto T . 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 . January 2001 . 11208867 . 2193341 . 10.1084/jem.193.2.263 .
• Bourette RP, De Sepulveda P, Arnaud S, Dubreuil P, Rottapel R, Mouchiroud G . 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 . June 2001 . 11297560 . 10.1074/jbc.M101878200 . free .
• Mooney RA, Senn J, Cameron S, Inamdar N, Boivin LM, Shang Y, Furlanetto RW . 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 . July 2001 . 11342531 . 10.1074/jbc.M010579200 . free .
• Bellezza I, Neuwirt H, Nemes C, Cavarretta IT, Puhr M, Steiner H, Minelli A, Bartsch G, Offner F, Hobisch A, Doppler W, Culig Z . 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 . December 2006 . 17148681 . 1762483 . 10.2353/ajpath.2006.060171 .
• Neuwirt H, Puhr M, Santer FR, Susani M, Doppler W, Marcias G, Rauch V, Brugger M, Hobisch A, Kenner L, Culig Z . 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 . May 2009 . 19342366 . 2671279 . 10.2353/ajpath.2009.080751 .

Notes and References

1. Yoshimura A, Ohkubo T, Kiguchi T, Jenkins NA, Gilbert DJ, Copeland NG, Hara T, Miyajima A . 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 . June 1995 . 7796808 . 398400 . 10.1002/j.1460-2075.1995.tb07281.x.
2. Minamoto S, Ikegame K, Ueno K, Narazaki M, Naka T, Yamamoto H, Matsumoto T, Saito H, Hosoe S, Kishimoto T . 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 . August 1997 . 9266833 . 10.1006/bbrc.1997.7080 .
3. Web site: OrthoMaM phylogenetic marker: SOCS1 coding sequence .
4. Web site: Entrez Gene: SOCS1 suppressor of cytokine signaling 1.
5. Charoenthongtrakul S, Zhou Q, Shembade N, Harhaj NS, Harhaj EW . 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 . July 2011 . 21593151 . 10.1128/JVI.00007-11 . 3126571 .
6. De Sepulveda P, Okkenhaug K, Rose JL, Hawley RG, Dubreuil P, Rottapel R . Socs1 binds to multiple signalling proteins and suppresses steel factor-dependent proliferation . The EMBO Journal . 18 . 4 . 904–15 . February 1999 . 10022833 . 1171183 . 10.1093/emboj/18.4.904 .
7. Bourette RP, De Sepulveda P, Arnaud S, Dubreuil P, Rottapel R, Mouchiroud G . 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 . June 2001 . 11297560 . 10.1074/jbc.M101878200 . free .
8. Ram PA, Waxman DJ . SOCS/CIS protein inhibition of growth hormone-stimulated STAT5 signaling by multiple mechanisms . The Journal of Biological Chemistry . 274 . 50 . 35553–61 . December 1999 . 10585430 . 10.1074/jbc.274.50.35553 . free .
9. Rui L, Yuan M, Frantz D, Shoelson S, White MF . 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 . November 2002 . 12228220 . 10.1074/jbc.C200444200 . free .
10. Yasukawa H, Misawa H, Sakamoto H, Masuhara M, Sasaki A, Wakioka T, Ohtsuka S, Imaizumi T, Matsuda T, Ihle JN, Yoshimura A . The JAK-binding protein JAB inhibits Janus tyrosine kinase activity through binding in the activation loop . The EMBO Journal . 18 . 5 . 1309–20 . March 1999 . 10064597 . 1171221 . 10.1093/emboj/18.5.1309 .
11. Dif F, Saunier E, Demeneix B, Kelly PA, Edery M . Cytokine-inducible SH2-containing protein suppresses PRL signaling by binding the PRL receptor . Endocrinology . 142 . 12 . 5286–93 . December 2001 . 11713228 . 10.1210/endo.142.12.8549 . free .
12. 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 . A new protein containing an SH2 domain that inhibits JAK kinases . Nature . 387 . 6636 . 921–4 . June 1997 . 9202126 . 10.1038/43213 . 1997Natur.387..921E . 4347361 . free .
13. Pezet A, Favre H, Kelly PA, Edery M . Inhibition and restoration of prolactin signal transduction by suppressors of cytokine signaling . The Journal of Biological Chemistry . 274 . 35 . 24497–502 . August 1999 . 10455112 . 10.1074/jbc.274.35.24497 . free .
14. Ungureanu D, Saharinen P, Junttila I, Hilton DJ, Silvennoinen O . Regulation of Jak2 through the ubiquitin-proteasome pathway involves phosphorylation of Jak2 on Y1007 and interaction with SOCS-1 . Molecular and Cellular Biology . 22 . 10 . 3316–26 . May 2002 . 11971965 . 133778 . 10.1128/mcb.22.10.3316-3326.2002 .
15. 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 . Cloning and characterization of novel CIS family genes . Biochemical and Biophysical Research Communications . 239 . 2 . 439–46 . October 1997 . 9344848 . 10.1006/bbrc.1997.7484 .
16. Ohya K, Kajigaya S, Yamashita Y, Miyazato A, Hatake K, Miura Y, Ikeda U, Shimada K, Ozawa K, Mano H . SOCS-1/JAB/SSI-1 can bind to and suppress Tec protein-tyrosine kinase . The Journal of Biological Chemistry . 272 . 43 . 27178–82 . October 1997 . 9341160 . 10.1074/jbc.272.43.27178 . free .