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Gene Review

SOCS1  -  suppressor of cytokine signaling 1

Homo sapiens

Synonyms: CIS1, CISH1, Cish1, JAB, JAK-binding protein, ...
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Disease relevance of SOCS1


High impact information on SOCS1

  • The CIS family of proteins (also referred to as the SOCS or SSI family) has been implicated in the regulation of signal transduction by a variety of cytokines [8].
  • Moreover, the restoration of SOCS-1 suppressed both growth rate and anchorage-independent growth of cells in which SOCS-1 was methylation-silenced and JAK2 was constitutively activated [9].
  • We identified aberrant methylation in the CpG island of SOCS-1 that correlated with its transcription silencing in HCC cell lines [9].
  • This growth suppression was caused by apoptosis and was reproduced by AG490, a specific, chemical JAK2 inhibitor that reversed constitutive phosphorylation of STAT3 in SOCS-1 inactivated cells [9].
  • Reconstitution of the lymphoid lineage of JAK3-deficient mice with SOCS1-deficient stem cells recapitulates the lethality and T cell alterations [10].

Chemical compound and disease context of SOCS1


Biological context of SOCS1


Anatomical context of SOCS1

  • Furthermore, the inhibition of SOCS in the cardiac myocyte through adeno-associated virus-mediated (AAV-mediated) expression of a dominant-negative SOCS1 increased the myocyte resistance to the acute cardiac injury caused by enteroviral infection [16].
  • This suggests an important role for JAB/SOCS1/SSI-1 in regulating T-cell responses [17].
  • The effect of the interaction between FGFR3 and SOCS1 on receptor activity was investigated in a chondrocytic cell line overexpressing SOCS1 [14].
  • Expression of osteopontin (OPN), which is directly upregulated by FGF in chondrocytes, was stimulated by lower levels of FGF in cells expressing SOCS1 compared with parental cells [14].
  • Using reverse transcriptase (RT)-PCR and Western blot analysis we investigated the expression of SOCS1, SOCS2, and SOCS3 mRNA and protein, respectively, by human villous placenta, amnion and choriodecidua (n = 3-4) [18].

Associations of SOCS1 with chemical compounds

  • Our study demonstrates the substrate-specific E3 ubiquitin-ligase-like activity of SOCS1 for activated JAK2 and may provide a novel strategy for the suppression of oncogenic tyrosine kinases [12].
  • Treatment of these cell lines with the demethylating agent 5-aza-2'-deoxycytidine (DAC) up-regulated SOCS-1 expression [19].
  • Mutation of receptor tyrosines 950, 1250, 1251, and 1316 to phenylalanine or deletion of the COOH-terminal 93 amino acids did not result in decreased interaction of the receptor with hSOCS-2 protein. hSOCS-1 protein also interacted strongly with IGF-IR in the two-hybrid assay [20].
  • In contrast, titanium inhibition of interferon-gamma signaling is not dependent on mitogen-activated protein kinase activation and is accompanied by only modest induction of the interferon-gamma inhibitor SOCS1 [21].
  • In addition, SOCS1, a negative regulator of IFNgamma signaling and which is degraded by the proteasome, was stabilized by ethanol treatment, presumably because of inhibited proteasome activity [22].

Physical interactions of SOCS1


Regulatory relationships of SOCS1


Other interactions of SOCS1


Analytical, diagnostic and therapeutic context of SOCS1


  1. Impaired IFN-gamma-dependent inflammatory responses in human keratinocytes overexpressing the suppressor of cytokine signaling 1. Federici, M., Giustizieri, M.L., Scarponi, C., Girolomoni, G., Albanesi, C. J. Immunol. (2002) [Pubmed]
  2. Expression of SOCS1 and SOCS3 genes is differentially regulated in breast cancer cells in response to proinflammatory cytokine and growth factor signals. Evans, M.K., Yu, C.R., Lohani, A., Mahdi, R.M., Liu, X., Trzeciak, A.R., Egwuagu, C.E. Oncogene (2007) [Pubmed]
  3. Differential hypermethylation of SOCS genes in ovarian and breast carcinomas. Sutherland, K.D., Lindeman, G.J., Choong, D.Y., Wittlin, S., Brentzell, L., Phillips, W., Campbell, I.G., Visvader, J.E. Oncogene (2004) [Pubmed]
  4. SOCS1 and SOCS3 are targeted by hepatitis C virus core/gC1qR ligation to inhibit T-cell function. Yao, Z.Q., Waggoner, S.N., Cruise, M.W., Hall, C., Xie, X., Oldach, D.W., Hahn, Y.S. J. Virol. (2005) [Pubmed]
  5. SOCS1-negative feedback of STAT1 activation is a key pathway in the dsRNA-induced innate immune response of human keratinocytes. Dai, X., Sayama, K., Yamasaki, K., Tohyama, M., Shirakata, Y., Hanakawa, Y., Tokumaru, S., Yahata, Y., Yang, L., Yoshimura, A., Hashimoto, K. J. Invest. Dermatol. (2006) [Pubmed]
  6. SOCS1 silencing enhances antitumor activity of type I IFNs by regulating apoptosis in neuroendocrine tumor cells. Zitzmann, K., Brand, S., De Toni, E.N., Baehs, S., Göke, B., Meinecke, J., Spöttl, G., Meyer, H.H., Auernhammer, C.J. Cancer Res. (2007) [Pubmed]
  7. Methylation of SOCS-3 and SOCS-1 in the carcinogenesis of Barrett's adenocarcinoma. Tischoff, I., Hengge, U.R., Vieth, M., Ell, C., Stolte, M., Weber, A., Schmidt, W.E., Tannapfel, A. Gut (2007) [Pubmed]
  8. Negative regulation of cytokine signaling pathways. Yasukawa, H., Sasaki, A., Yoshimura, A. Annu. Rev. Immunol. (2000) [Pubmed]
  9. SOCS-1, a negative regulator of the JAK/STAT pathway, is silenced by methylation in human hepatocellular carcinoma and shows growth-suppression activity. Yoshikawa, H., Matsubara, K., Qian, G.S., Jackson, P., Groopman, J.D., Manning, J.E., Harris, C.C., Herman, J.G. Nat. Genet. (2001) [Pubmed]
  10. SOCS1 deficiency causes a lymphocyte-dependent perinatal lethality. Marine, J.C., Topham, D.J., McKay, C., Wang, D., Parganas, E., Stravopodis, D., Yoshimura, A., Ihle, J.N. Cell (1999) [Pubmed]
  11. Aberrant methylation of suppressor of cytokine signalling-1 (SOCS-1) gene in pancreatic ductal neoplasms. Fukushima, N., Sato, N., Sahin, F., Su, G.H., Hruban, R.H., Goggins, M. Br. J. Cancer (2003) [Pubmed]
  12. The SOCS box of SOCS-1 accelerates ubiquitin-dependent proteolysis of TEL-JAK2. Kamizono, S., Hanada, T., Yasukawa, H., Minoguchi, S., Kato, R., Minoguchi, M., Hattori, K., Hatakeyama, S., Yada, M., Morita, S., Kitamura, T., Kato, H., Nakayama Ki, n.u.l.l., Yoshimura, A. J. Biol. Chem. (2001) [Pubmed]
  13. CXCR4-mediated suppressor of cytokine signaling up-regulation inactivates growth hormone function. Garzón, R., Soriano, S.F., Rodríguez-Frade, J.M., Gómez, L., Martín de Ana, A., Sánchez-Gómez, M., Martínez-A, C., Mellado, M. J. Biol. Chem. (2004) [Pubmed]
  14. Suppressors of cytokine signaling (SOCS) 1 and SOCS3 interact with and modulate fibroblast growth factor receptor signaling. Ben-Zvi, T., Yayon, A., Gertler, A., Monsonego-Ornan, E. J. Cell. Sci. (2006) [Pubmed]
  15. Radiation hybrid and cytogenetic mapping of SOCS1 and SOCS2 to chromosomes 16p13 and 12q, respectively. Yandava, C.N., Pillari, A., Drazen, J.M. Genomics (1999) [Pubmed]
  16. The suppressor of cytokine signaling-1 (SOCS1) is a novel therapeutic target for enterovirus-induced cardiac injury. Yasukawa, H., Yajima, T., Duplain, H., Iwatate, M., Kido, M., Hoshijima, M., Weitzman, M.D., Nakamura, T., Woodard, S., Xiong, D., Yoshimura, A., Chien, K.R., Knowlton, K.U. J. Clin. Invest. (2003) [Pubmed]
  17. JAB/SOCS1/SSI-1 is an interleukin-2-induced inhibitor of IL-2 signaling. Sporri, B., Kovanen, P.E., Sasaki, A., Yoshimura, A., Leonard, W.J. Blood (2001) [Pubmed]
  18. Identification of suppressors of cytokine signaling (SOCS) proteins in human gestational tissues: differential regulation is associated with the onset of labor. Blumenstein, M., Bowen-Shauver, J.M., Keelan, J.A., Mitchell, M.D. J. Clin. Endocrinol. Metab. (2002) [Pubmed]
  19. SOCS-1, a negative regulator of cytokine signaling, is frequently silenced by methylation in multiple myeloma. Galm, O., Yoshikawa, H., Esteller, M., Osieka, R., Herman, J.G. Blood (2003) [Pubmed]
  20. Interaction of human suppressor of cytokine signaling (SOCS)-2 with the insulin-like growth factor-I receptor. Dey, B.R., Spence, S.L., Nissley, P., Furlanetto, R.W. J. Biol. Chem. (1998) [Pubmed]
  21. Wear debris inhibition of anti-osteoclastogenic signaling by interleukin-6 and interferon-gamma. Mechanistic insights and implications for periprosthetic osteolysis. Rakshit, D.S., Ly, K., Sengupta, T.K., Nestor, B.J., Sculco, T.P., Ivashkiv, L.B., Purdue, P.E. The Journal of bone and joint surgery. American volume. (2006) [Pubmed]
  22. Ethanol metabolism alters interferon gamma signaling in recombinant HepG2 cells. Osna, N.A., Clemens, D.L., Donohue, T.M. Hepatology (2005) [Pubmed]
  23. STAT6 and Ets-1 form a stable complex that modulates Socs-1 expression by interleukin-4 in keratinocytes. Travagli, J., Letourneur, M., Bertoglio, J., Pierre, J. J. Biol. Chem. (2004) [Pubmed]
  24. COMMD1 promotes the ubiquitination of NF-kappaB subunits through a cullin-containing ubiquitin ligase. Maine, G.N., Mao, X., Komarck, C.M., Burstein, E. EMBO J. (2007) [Pubmed]
  25. Regulation of Jak2 through the ubiquitin-proteasome pathway involves phosphorylation of Jak2 on Y1007 and interaction with SOCS-1. Ungureanu, D., Saharinen, P., Junttila, I., Hilton, D.J., Silvennoinen, O. Mol. Cell. Biol. (2002) [Pubmed]
  26. SOCS1 inhibits tumor necrosis factor-induced activation of ASK1-JNK inflammatory signaling by mediating ASK1 degradation. He, Y., Zhang, W., Zhang, R., Zhang, H., Min, W. J. Biol. Chem. (2006) [Pubmed]
  27. The janus kinase inhibitor, Jab/SOCS-1, is an interferon-gamma inducible gene and determines the sensitivity to interferons. Sakamoto, H., Kinjyo, I., Yoshimura, A. Leuk. Lymphoma (2000) [Pubmed]
  28. SOCS-1/JAB/SSI-1 can bind to and suppress Tec protein-tyrosine kinase. Ohya, K., Kajigaya, S., Yamashita, Y., Miyazato, A., Hatake, K., Miura, Y., Ikeda, U., Shimada, K., Ozawa, K., Mano, H. J. Biol. Chem. (1997) [Pubmed]
  29. Estrogen inhibits GH signaling by suppressing GH-induced JAK2 phosphorylation, an effect mediated by SOCS-2. Leung, K.C., Doyle, N., Ballesteros, M., Sjogren, K., Watts, C.K., Low, T.H., Leong, G.M., Ross, R.J., Ho, K.K. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  30. Downregulation of IL-6-induced STAT3 tyrosine phosphorylation by TGF-beta1 is mediated by caspase-dependent and -independent processes. Wierenga, A.T., Schuringa, J.J., Eggen, B.J., Kruijer, W., Vellenga, E. Leukemia (2002) [Pubmed]
  31. SOCS-3 is frequently methylated in head and neck squamous cell carcinoma and its precursor lesions and causes growth inhibition. Weber, A., Hengge, U.R., Bardenheuer, W., Tischoff, I., Sommerer, F., Markwarth, A., Dietz, A., Wittekind, C., Tannapfel, A. Oncogene (2005) [Pubmed]
  32. Structural basis for phosphotyrosine recognition by suppressor of cytokine signaling-3. Bergamin, E., Wu, J., Hubbard, S.R. Structure (2006) [Pubmed]
  33. SOCS1 methylation in patients with newly diagnosed acute myeloid leukemia. Chen, C.Y., Tsay, W., Tang, J.L., Shen, H.L., Lin, S.W., Huang, S.Y., Yao, M., Chen, Y.C., Shen, M.C., Wang, C.H., Tien, H.F. Genes Chromosomes Cancer (2003) [Pubmed]
  34. An alternative and effective HIV vaccination approach based on inhibition of antigen presentation attenuators in dendritic cells. Song, X.T., Evel-Kabler, K., Rollins, L., Aldrich, M., Gao, F., Huang, X.F., Chen, S.Y. PLoS Med. (2006) [Pubmed]
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