Submit
Search
Submit
Menu

  • Information

  • References

  • Contents

  • [1]J. Lotem and L. Sachs: Cytokine control of developmental programs in normal hematopoiesis and leukemia. Oncogene 21, 3284–3294 (2002)

  • [2]K. Inagaki-Ohara, T. Kondo, M. Ito, and A. Yoshimura: SOCS, inflammation, and cancer. JAK-STAT 2, e24053 (2013)

  • [3]B.T. Kile, B.A. Schulman, W.S. Alexander, N.A. Nicola, H.M.E. Martin, and D.J. Hilton: The SOCS box: a tale of destruction and degradation. Trends Biochem. Sci. 27, 235–241 (2002)

  • [4]T. Kamura, K. Maenaka, S. Kotoshiba, M. Matsumoto, D. Kohda, R.C. Conaway, J.W. Conaway, and K.I. Nakayama: VHL-box and SOCS-box domains determine binding specificity for Cul2-Rbx1 and Cul5-Rbx2 modules of ubiquitin ligases. Genes Dev. 18, 3055–3065 (2004)

  • [5]D.J. Hilton, R.T. Richardson, W.S. Alexander, E.M. Viney, T.A. Willson, N.S. Sprigg, R. Starr, S.E. Nicholson, D. Metcalf, and N.A. Nicola: Twenty proteins containing a C-terminal SOCS box form five structural classes. Proc. Natl. Acad. Sci. U. S. A. 95, 114–119 (1998)

  • [6]G.M. Tannahill, J. Elliott, A.C. Barry, L. Hibbert, N.A. Cacalano, and J.A. Johnston: SOCS2 can enhance interleukin-2 (IL-2) and IL-3 signaling by accelerating SOCS3 degradation. Mol. Cell. Biol. 25, 9115–9126 (2005)

  • [7]J. Piessevaux, D. Lavens, T. Montoye, J. Wauman, D. Catteeuw, J. Vandekerckhove, D. Belsham, F. Peelman, and J. Tavernier: Functional cross-modulation between SOCS proteins can stimulate cytokine signaling. J. Biol. Chem. 281, 32953–32966 (2006)

  • [8]R. Starr, T.A. Willson, E.M. Viney, L.J. Murray, J.R. Rayner, B.J. Jenkins, T.J. Gonda, W.S. Alexander, D. Metcalf, N.A. Nicola, and D.J. Hilton: A family of cytokine-inducible inhibitors of signalling. Nature 387, 917–921 (1997)

  • [9]D. Metcalf, C.J. Greenhalgh, E. Viney, T.A. Willson, R. Starr, N.A. Nicola, D.J. Hilton, and W.S. Alexander: Gigantism in mice lacking suppressor of cytokine signalling-2. Nature 405, 1069–1073 (2000)

  • [10]A. Pezet, H. Favre, P.A. Kelly, and M. Edery: Inhibition and restoration of prolactin signal transduction by suppressors of cytokine signaling. J. Biol. Chem. 274, 24497–24502 (1999)

  • [11]S. Minamoto, K. Ikegame, K. Ueno, M. Narazaki, T. Naka, H. Yamamoto, T. Matsumoto, H. Saito, S. Hosoe, and T. Kishimoto: Cloning and functional analysis of new members of STAT induced STAT inhibitor (SSI) family: SSI-2 and SSI-3. Biochem. Biophys. Res. Commun. 237, 79–83 (1997)

  • [12]D.L. Krebs and D.J. Hilton: SOCS proteins: negative regulators of cytokine signaling. Stem Cells 19, 378–387 (2001)

  • [13]B.R. Dey, S.L. Spence, P. Nissley, and R.W. Furlanetto: Interaction of human suppressor of cytokine signaling (SOCS)-2 with the insulin-like growth factor-I receptor. J. Biol. Chem. 273, 24095–24101 (1998)

  • [14]S.E. Nicholson, T.A. Willson, A. Farley, R. Starr, J.G. Zhang, M. Baca, W.S. Alexander, D. Metcalf, D.J. Hilton, and N.A. Nicola: Mutational analyses of the SOCS proteins suggest a dual domain requirement but distinct mechanisms for inhibition of LIF and IL-6 signal transduction. EMBO J. 18, 375–385 (1999)

  • [15]P.A. Ram and D.J. Waxman: SOCS/CIS protein inhibition of growth hormone-stimulated STAT5 signaling by multiple mechanisms. J. Biol. Chem. 274, 35553–35561 (1999)

  • [16]M. Vesterlund, F. Zadjali, T. Persson, M.L. Nielsen, B.M. Kessler, G. Norstedt, and A. Flores-Morales: The SOCS2 ubiquitin ligase complex regulates growth hormone receptor levels. PLoS One 6, e25358 (2011)

  • [17]S. Horvat and J.F. Medrano: Lack of Socs2 expression causes the high-growth phenotype in mice. Genomics 72, 209–212 (2001)

  • [18]C.J. Greenhalgh, E. Rico-bautista, M. Lorentzon, A.L. Thaus, P.O. Morgan, T.A. Willson, P. Zervoudakis, D. Metcalf, I. Street, N.A. Nicola, A.D. Nash, L.J. Fabri, G. Norstedt, C. Ohlsson, A. Flores-morales, W.S. Alexander, and D.J. Hilton: SOCS2 negatively regulates growth hormone action in vitro and in vivo. J. Clin. Invest. 115, 397–406 (2005)

  • [19]C.J. Greenhalgh, P. Bertolino, S.L. Asa, D. Metcalf, J.E. Corbin, T.E. Adams, H.W. Davey, N.A. Nicola, D.J. Hilton, and W.S. Alexander: Growth enhancement in suppressor of cytokine signaling 2 (SOCS-2)-deficient mice is dependent on signal transducer and activator of transcription 5b (STAT5b). Mol. Endocrinol. 16, 1394–1406 (2002)

  • [20]J.A. Hansen, K. Lindberg, D.J. Hilton, J.H. Nielsen, and N. Billestrup: Mechanism of inhibition of growth hormone receptor signaling by suppressor of cytokine signaling proteins. Mol. Endocrinol. 13, 1832–1843 (1999)

  • [21]H. Favre, A. Benhamou, J. Finidori, P.A. Kelly, and M. Edery: Dual effects of suppressor of cytokine signaling (SOCS-2) on growth hormone signal transduction. FEBS Lett. 453, 63–66 (1999)

  • [22]C.J. Greenhalgh, D. Metcalf, A.L. Thaus, J.E. Corbin, R. Uren, P.O. Morgan, L.J. Fabri, J.G. Zhang, H.M. Martin, T.A. Willson, N. Billestrup, N.A. Nicola, M. Baca, W.S. Alexander, and D.J. Hilton: Biological evidence that SOCS-2 can act either as an enhancer or suppressor of growth hormone signaling. J. Biol. Chem. 277, 40181–40184 (2002)

  • [23]F. Bogazzi, F. Ultimieri, F. Raggi, D. Russo, A. Costa, E. Marciano, L. Bartalena, and E. Martino: Changes in the expression of suppressor of cytokine signalling (SOCS) 2 in the colonic mucosa of acromegalic patients are associated with hyperplastic polyps. Clin. Endocrinol. (Oxf). 70, 898–906 (2009)

  • [24]H. Kiu, C.J. Greenhalgh, A. Thaus, D.J. Hilton, N.A. Nicola, W.S. Alexander, and A.W. Roberts: Regulation of multiple cytokine signalling pathways by SOCS3 is independent of SOCS2. Growth Factors 27, 384–393 (2009)

  • [25]J.U. Kazi and L. Rönnstrand: Suppressor of cytokine signaling 2 (SOCS2) associates with FLT3 and negatively regulates downstream signaling. Mol. Oncol. 7, 693–703 (2013)

  • [26]I.D. Dimitriou, L. Clemenza, A.J. Scotter, G. Chen, F.M. Guerra, and R. Rottapel: Putting out the fire: Coordinated suppression of the innate and adaptive immune systems by SOCS1 and SOCS3 proteins. Immunol. Rev. 224, 265–283 (2008)

  • [27]D.C. Palmer and N.P. Restifo: Suppressors of cytokine signaling (SOCS) in T cell differentiation, maturation, and function. Trends Immunol. 30, 592–602 (2009)

  • [28]G. Posselt, H. Schwarz, A. Duschl, and J. Horejs-Hoeck: Suppressor of cytokine signaling 2 is a feedback inhibitor of TLR-induced activation in human monocyte-derived dendritic cells. J. Immunol. 187, 2875–2884 (2011)

  • [29]H. Schwarz, G. Posselt, P. Wurm, M. Ulbing, A. Duschl, and J. Horejs-Hoeck: TLR8 and NOD signaling synergistically induce the production of IL-1beta and IL-23 in monocyte-derived DCs and enhance the expression of the feedback inhibitor SOCS2. Immunobiology 218, 533–542 (2013)

  • [30]J. Hu, D. Lou, B. Carow, M.E. Winerdal, M. Rottenberg, A.C. Wikström, G. Norstedt, and O. Winqvist: LPS regulates SOCS2 transcription in a type I interferon dependent autocrine-paracrine loop. PLoS One 7, e30166 (2012)

  • [31]S.H. Lee, S. Yun, Z.H. Piao, M. Jeong, D.O. Kim, H. Jung, J. Lee, M.J. Kim, M.S. Kim, J.W. Chung, T.D. Kim, S.R. Yoon, P.D. Greenberg, and I. Choi: Suppressor of cytokine signaling 2 regulates IL-15-primed human NK cell function via control of phosphorylated Pyk2. J. Immunol. 185, 917–928 (2010)

  • [32]B.A. Croker, H. Kiu, and S.E. Nicholson: SOCS regulation of the JAK/STAT signalling pathway. Semin. Cell Dev. Biol. 19, 414–422 (2008)

  • [33]C. a Knosp, H.P. Carroll, J. Elliott, S.P. Saunders, H.J. Nel, S. Amu, J.C. Pratt, S. Spence, E. Doran, N. Cooke, R. Jackson, J. Swift, D.C. Fitzgerald, L.G. Heaney, P.G. Fallon, A. Kissenpfennig, and J. a Johnston: SOCS2 regulates T helper type 2 differentiation and the generation of type 2 allergic responses. J. Exp. Med. 208, 1523–1531 (2011)

  • [34]J. Zhu and W.E. Paul: Peripheral CD4+ T-cell differentiation regulated by networks of cytokines and transcription factors. Immunol. Rev. 238, 247–262 (2010)

  • [35]Z. Chen, A. Laurence, Y. Kanno, M. Pacher-Zavisin, B.M. Zhu, C. Tato, A. Yoshimura, L. Hennighausen, and J.J. O’Shea: Selective regulatory function of Socs3 in the formation of IL-17-secreting T cells. Proc. Natl. Acad. Sci. U. S. A. 103, 8137–8142 (2006)

  • [36]Y. Seki, H. Inoue, N. Nagata, K. Hayashi, S. Fukuyama, K. Matsumoto, O. Komine, S. Hamano, K. Himeno, K. Inagaki-Ohara, N. Cacalano, A. O’Garra, T. Oshida, H. Saito, J.A. Johnston, A. Yoshimura, and M. Kubo: SOCS-3 regulates onset and maintenance of T(H)2-mediated allergic responses. Nat. Med. 9, 1047–1054 (2003)

  • [37]F.S. Machado, J.E. Johndrow, L. Esper, A. Dias, A. Bafica, C.N. Serhan, and J. Aliberti: Anti-inflammatory actions of lipoxin A4 and aspirin-triggered lipoxin are SOCS-2 dependent. Nat. Med. 12, 330–334 (2006)

  • [38]X. Zhou, S. Bailey-Bucktrout, L.T. Jeker, and J.A. Bluestone: Plasticity of CD4(+) FoxP3(+) T cells. Curr. Opin. Immunol. 21, 281–285 (2009)

  • [39]N. Komatsu, M.E. Mariotti-Ferrandiz, Y. Wang, B. Malissen, H. Waldmann, and S. Hori: Heterogeneity of natural Foxp3+ T cells: a committed regulatory T-cell lineage and an uncommitted minor population retaining plasticity. Proc. Natl. Acad. Sci. U. S. A. 106, 1903–1908 (2009)

  • [40]X.O. Yang, R. Nurieva, G.J. Martinez, H.S. Kang, Y. Chung, B.P. Pappu, B. Shah, S.H. Chang, K.S. Schluns, S.S. Watowich, X.H. Feng, A.M. Jetten, and C. Dong: Molecular antagonism and plasticity of regulatory and inflammatory T cell programs. Immunity 29, 44–56 (2008)

  • [41]C.A. Knosp, C. Schiering, S. Spence, H.P. Carroll, H.J. Nel, M. Osbourn, R. Jackson, O. Lyubomska, B. Malissen, R. Ingram, D.C. Fitzgerald, F. Powrie, P.G. Fallon, J.A. Johnston, and A. Kissenpfennig: Regulation of Foxp3+ inducible regulatory T cell stability by SOCS2. J. Immunol. 190, 3235–3245 (2013)

  • [42]D. Mucida, N. Kutchukhidze, A. Erazo, M. Russo, J.J. Lafaille, and M.A. Curotto de Lafaille: Oral tolerance in the absence of naturally occurring Tregs. J. Clin. Invest. 115, 1923–1933 (2005)

  • [43]M.A. Curotto de Lafaille, N. Kutchukhidze, S. Shen, Y. Ding, H. Yee, and J.J. Lafaille: Adaptive Foxp3+ regulatory T cell-dependent and -independent control of allergic inflammation. Immunity 29, 114–126 (2008)

  • [44]S.Z. Josefowicz, R.E. Niec, H.Y. Kim, P. Treuting, T. Chinen, Y. Zheng, D.T. Umetsu, and A.Y. Rudensky: Extrathymically generated regulatory T cells control mucosal TH2 inflammation. Nature 482, 395–399 (2012)

  • [45]M.C. de Andrés, K. Imagawa, K. Hashimoto, A. Gonzalez, M.B. Goldring, H.I. Roach, and R.O.C. Oreffo: Suppressors of cytokine signalling (SOCS) are reduced in osteoarthritis. Biochem. Biophys. Res. Commun. 407, 54–59 (2011)

  • [46]J.T. Tsao, C.C. Kuo, and S.C. Lin: The analysis of CIS, SOCS1, SOSC2 and SOCS3 transcript levels in peripheral blood mononuclear cells of systemic lupus erythematosus and rheumatoid arthritis patients. Clin. Exp. Med. 8, 179–185 (2008)

  • [47]P. Isomäki, T. Alanärä, P. Isohanni, a. Lagerstedt, M. Korpela, T. Moilanen, T. Visakorpi, and O. Silvennoinen: The expression of SOCS is altered in rheumatoid arthritis. Rheumatology 46, 1538–1546 (2007)

  • [48]M. Federici, M.L. Giustizieri, C. Scarponi, G. Girolomoni, and C. Albanesi: Impaired IFN-gamma-dependent inflammatory responses in human keratinocytes overexpressing the suppressor of cytokine signaling 1. J. Immunol. 169, 434–442 (2002)

  • [49]C. Santangelo, A. Scipioni, L. Marselli, P. Marchetti, and F. Dotta: Suppressor of cytokine signaling gene expression in human pancreatic islets: modulation by cytokines. Eur. J. Endocrinol. 152, 485–489 (2005)

  • [50]H. Kato, K. Nomura, D. Osabe, S. Shinohara, O. Mizumori, R. Katashima, S. Iwasaki, K. Nishimura, M. Yoshino, M. Kobori, E. Ichiishi, N. Nakamura, T. Yoshikawa, T. Tanahashi, P. Keshavarz, K. Kunika, M. Moritani, E. Kudo, K. Tsugawa, Y. Takata, D. Hamada, N. Yasui, T. Miyamoto, H. Shiota, H. Inoue, and M. Itakura: Association of single-nucleotide polymorphisms in the suppressor of cytokine signaling 2 (SOCS2) gene with type 2 diabetes in the Japanese. Genomics 87, 446–458 (2006)

  • [51]R. Puff, P. Dames, M. Weise, B. Göke, K.G. Parhofer, and A. Lechner: No non-redundant function of suppressor of cytokine signaling 2 in insulin producing beta -cells. Islets 2, 252–257 (2010)

  • [52]A. Rasche, H. Al-Hasani, and R. Herwig: Meta-analysis approach identifies candidate genes and associated molecular networks for type-2 diabetes mellitus. BMC Genomics 9, 310 (2008)

  • [53]P. Lebrun, E. Cognard, P. Gontard, R. Bellon-Paul, C. Filloux, M.F. Berthault, C. Magnan, J. Ruberte, M. Luppo, a. Pujol, N. Pachera, a. Herchuelz, F. Bosch, and E. Van Obberghen: The suppressor of cytokine signalling 2 (SOCS2) is a key repressor of insulin secretion. Diabetologia 53, 1935–1946 (2010)

  • [54]N.A. Cacalano, D. Sanden, and J.A. Johnston: Tyrosine-phosphorylated SOCS-3 inhibits STAT activation but binds to p120 RasGAP and activates Ras. Nat. Cell Biol. 3, 460–465 (2001)

  • [55]P. De Sepulveda, K. Okkenhaug, J. La Rose, R.G. Hawley, P. Dubreuil, and R. Rottapel: Socs1 binds to multiple signalling proteins and suppresses Steel factor-dependent proliferation. EMBO J. 18, 904–915 (1999)

  • [56]P. De Sepulveda, S. Ilangumaran, and R. Rottapel: Suppressor of cytokine signaling-1 inhibits VAV function through protein degradation. J. Biol. Chem. 275, 14005–14008 (2000)

  • [57]R.T. Uren and A.M. Turnley: Regulation of neurotrophin receptor (Trk) signaling: suppressor of cytokine signaling 2 (SOCS2) is a new player. Front. Mol. Neurosci. 7, 39 (2014)

  • [58]M.N. Polizzotto, P.F. Bartlett, and A.M. Turnley: Expression of “suppressor of cytokine signalling” (SOCS) genes in the developing and adult mouse nervous system. J. Comp. Neurol. 423, 348–358 (2000)

  • [59]M.I. Ransome, Y. Goldshmit, P.F. Bartlett, M.J. Waters, and A.M. Turnley: Comparative analysis of CNS populations in knockout mice with altered growth hormone responsiveness. Eur. J. Neurosci. 19, 2069–2079 (2004)

  • [60]M.I. Ransome and A.M. Turnley: Analysis of neuronal subpopulations in mice over-expressing suppressor of cytokine signaling-2. Neuroscience 132, 673–687 (2005)

  • [61]M.I. Ransome and A.M. Turnley: Growth hormone signaling and hippocampal neurogenesis: insights from genetic models. Hippocampus 18, 1034–1050 (2008)

  • [62]A.M. Turnley, C.H. Faux, R.L. Rietze, J.R. Coonan, and P.F. Bartlett: Suppressor of cytokine signaling 2 regulates neuronal differentiation by inhibiting growth hormone signaling. Nat. Neurosci. 5, 1155–1162 (2002)

  • [63]Y. Goldshmit, C.E. Walters, H.J. Scott, C.J. Greenhalgh, and A.M. Turnley: SOCS2 induces neurite outgrowth by regulation of epidermal growth factor receptor activation. J. Biol. Chem. 279, 16349–16355 (2004)

  • [64]Y. Goldshmit, C.J. Greenhalgh, and A.M. Turnley: Suppressor of cytokine signalling-2 and epidermal growth factor regulate neurite outgrowth of cortical neurons. Eur. J. Neurosci. 20, 2260–2266 (2004)

  • [65]R.T. Uren, A. Turbić, A.W. Wong, R. Klein, S.S. Murray, and A.M. Turnley: A novel role of suppressor of cytokine signaling-2 in the regulation of TrkA neurotrophin receptor biology. J. Neurochem. 129, 614–627 (2014)

  • [66]L. Wang, Z. Zhang, R. Zhang, M.S. Hafner, H.K. Wong, Z. Jiao, and M. Chopp: Erythropoietin up-regulates SOCS2 in neuronal progenitor cells derived from SVZ of adult rat. Neuroreport 15, 1225–1229 (2004)

  • [67]Y. Kasagi, R. Tokita, T. Nakata, T. Imaki, and S. Minami: Human growth hormone induces SOCS3 and CIS mRNA increase in the hypothalamic neurons of hypophysectomized rats. Endocr. J. 51, 145–154 (2004)

  • [68]H.J. Scott, M.J. Stebbing, C.E. Walters, S. McLenachan, M.I. Ransome, N.R. Nichols, and A.M. Turnley: Differential effects of SOCS2 on neuronal differentiation and morphology. Brain Res. 1067, 138–145 (2006)

  • [69]K.K. Park, Y. Hu, J. Muhling, M.A. Pollett, E.J. Dallimore, A.M. Turnley, Q. Cui, and A.R. Harvey: Cytokine-induced SOCS expression is inhibited by cAMP analogue: impact on regeneration in injured retina. Mol. Cell. Neurosci. 41, 313–324 (2009)

  • [70]J.S. Choi, Y.J. Shin, J.Y. Lee, J.Y. Choi, J.H. Cha, M.H. Chun, and M.Y. Lee: Enhanced expression of SOCS-2 in the rat hippocampus after transient forebrain ischemia. J. Neurotrauma 26, 2097–2106 (2009)

  • [71]U. Ratnayake, H.S. Basrai, A.M. Turnley, and M. van den Buuse: Dopaminergic activity and behaviour in SOCS2 transgenic mice: Revealing a potential drug target for schizophrenia. Prog. Neuropsychopharmacol. Biol. Psychiatry 56, 247–253 (2015)

  • [72]Z. Culig: Suppressors of cytokine signalling-3 and -1 in human carcinogenesis. Front. Biosci. (Schol. Ed). 5, 277–283 (2013)

  • [73]J. Elliott, M.B. Hookham, and J.A. Johnston: The suppressors of cytokine signalling E3 ligases behave as tumour suppressors. Biochem. Soc. Trans. 36, 464–468 (2008)

  • [74]M.C. Trengove and A.C. Ward: SOCS proteins in development and disease. Am. J. Clin. Exp. Immunol. 2, 1–29 (2013)

  • [75]K.D. Sutherland, G.J. Lindeman, D.Y.H. Choong, S. Wittlin, L. Brentzell, W. Phillips, I.G. Campbell, and J.E. Visvader: Differential hypermethylation of SOCS genes in ovarian and breast carcinomas. Oncogene 23, 7726–7733 (2004)

  • [76]F. Farabegoli, C. Ceccarelli, D. Santini, and M. Taffurelli: Suppressor of cytokine signalling 2 (SOCS-2) expression in breast carcinoma. J. Clin. Pathol. 58, 1046–1050 (2005)

  • [77]X. Qiu, J. Zheng, X. Guo, X. Gao, H. Liu, Y. Tu, and Y. Zhang: Reduced expression of SOCS2 and SOCS6 in hepatocellular carcinoma correlates with aggressive tumor progression and poor prognosis. Mol. Cell. Biochem. 378, 99–106 (2013)

  • [78]J. guo Zhu, Q. shan Dai, Z. dong Han, H. chan He, R. jun Mo, G. Chen, Y. fei Chen, Y. ding Wu, S. bang Yang, F. neng Jiang, W. hong Chen, Z. lin Sun, and W. de Zhong: Expression of SOCSs in human prostate cancer and their association in prognosis. Mol. Cell. Biochem. 381, 51–59 (2013)

  • [79]M.C. Haffner, B. Petridou, J.P. Peyrat, F. Révillion, E. Müller-Holzner, G. Daxenbichler, C. Marth, and W. Doppler: Favorable prognostic value of SOCS2 and IGF-I in breast cancer. BMC Cancer 7, 136 (2007)

  • [80]H. Wikman, E. Kettunen, J.K. Seppänen, A. Karjalainen, J. Hollmén, S. Anttila, and S. Knuutila: Identification of differentially expressed genes in pulmonary adenocarcinoma by using cDNA array. Oncogene 21, 5804–5813 (2002)

  • [81]B. Schultheis, M. Carapeti-Marootian, A. Hochhaus, A. Weisser, J.M. Goldman, and J. V Melo: Overexpression of SOCS-2 in advanced stages of chronic myeloid leukemia: possible inadequacy of a negative feedback mechanism. Blood 99, 1766–1775 (2002)

  • [82]N. Hansen, H. Ågerstam, M. Wahlestedt, N. Landberg, M. Askmyr, M. Ehinger, M. Rissler, H. Lilljebjörn, P. Johnels, J. Ishiko, J. V Melo, W.S. Alexander, D. Bryder, M. Järås, and T. Fioretos: SOCS2 is dispensable for BCR/ABL1-induced chronic myeloid leukemia-like disease and for normal hematopoietic stem cell function. Leukemia 27, 130–135 (2013)

  • [83]W. Sasi, W.G. Jiang, A. Sharma, and K. Mokbel: Higher expression levels of SOCS 1,3,4,7 are associated with earlier tumour stage and better clinical outcome in human breast cancer. BMC Cancer 10, 178 (2010)

  • [84]M.L. Slattery, A. Lundgreen, L.M. Hines, G. Torres-Mejia, R.K. Wolff, M.C. Stern, and E.M. John: Genetic variation in the JAK/STAT/SOCS signaling pathway influences breast cancer-specific mortality through interaction with cigarette smoking and use of aspirin/NSAIDs: the Breast Cancer Health Disparities Study. Breast Cancer Res. Treat. 147, 145–158 (2014)

  • [85]P.J.M. Hendriksen, N.F.J. Dits, K. Kokame, A. Veldhoven, W.M. van Weerden, C.H. Bangma, J. Trapman, and G. Jenster: Evolution of the androgen receptor pathway during progression of prostate cancer. Cancer Res. 66, 5012–5020 (2006)

  • [86]D. Iglesias-Gato, Y.C. Chuan, P. Wikström, S. Augsten, N. Jiang, Y. Niu, A. Seipel, D. Danneman, M. Vermeij, L. Fernandez-Perez, G. Jenster, L. Egevad, G. Norstedt, and A. Flores-Morales: SOCS2 mediates the cross talk between androgen and growth hormone signaling in prostate cancer. Carcinogenesis 35, 24–33 (2014)

  • [87]J. Hoefer, J. Kern, P. Ofer, I.E. Eder, G. Schäfer, D. Dietrich, G. Kristiansen, S. Geley, J. Rainer, E. Gunsilius, H. Klocker, Z. Culig, and M. Puhr: SOCS2 correlates with malignancy and exerts growth promoting effects in prostate cancer. Endocr. Relat. Cancer 21, 175–187 (2013)

  • [88]E. Letellier, M. Schmitz, K. Baig, N. Beaume, C. Schwartz, S. Frasquilho, L. Antunes, N. Marcon, P. V Nazarov, L. Vallar, J. Even, and S. Haan: Identification of SOCS2 and SOCS6 as biomarkers in human colorectal cancer. Br. J. Cancer 111, 726–735 (2014)

  • [89]D. Sonkin, M. Palmer, X. Rong, K. Horrigan, C.H. Regnier, C. Fanton, J. Holash, M. Pinzon-Ortiz, M. Squires, A. Sirulnik, T. Radimerski, R. Schlegel, M. Morrissey, and Z.A. Cao: The identification and characterization of a STAT5 gene signature in hematologic malignancies. Cancer Biomark. 15, 79–87 (2015)

  • [90]C.Z. Michaylira, N.M. Ramocki, J.G. Simmons, C.K. Tanner, K.K. McNaughton, J.T. Woosley, C.J. Greenhalgh, and P.K. Lund: Haplotype insufficiency for suppressor of cytokine signaling-2 enhances intestinal growth and promotes polyp formation in growth hormone-transgenic mice. Endocrinology 147, 1632–1641 (2006)

  • [91]V. a Newton, N.M. Ramocki, B.P. Scull, J.G. Simmons, K. McNaughton, and P.K. Lund: Suppressor of cytokine signaling-2 gene disruption promotes Apc(Min/+) tumorigenesis and activator protein-1 activation. Am. J. Pathol. 176, 2320–2332 (2010)

  • [92]M.E. Miller, C.Z. Michaylira, J.G. Simmons, D.M. Ney, E.M. Dahly, J.K. Heath, and P.K. Lund: Suppressor of cytokine signaling-2: a growth hormone-inducible inhibitor of intestinal epithelial cell proliferation. Gastroenterology 127, 570–581 (2004)

  • [93]H. Fiegl, C. Gattringer, A. Widschwendter, A. Schneitter, A. Ramoni, D. Sarlay, I. Gaugg, G. Goebel, H.M. Müller, E. Mueller-Holzner, C. Marth, and M. Widschwendter: Methylated DNA collected by tampons--a new tool to detect endometrial cancer. Cancer Epidemiol. Biomarkers Prev. 13, 882–888 (2004)

  • [94]A. Marini, A. Mirmohammadsadegh, S. Nambiar, A. Gustrau, T. Ruzicka, and U.R. Hengge: Epigenetic inactivation of tumor suppressor genes in serum of patients with cutaneous melanoma. J. Invest. Dermatol. 126, 422–431 (2006)

  • [95]S. Liu, S. Ren, P. Howell, O. Fodstad, and A.I. Riker: Identification of novel epigenetically modified genes in human melanoma via promoter methylation gene profiling. Pigment Cell Melanoma Res. 21, 545–558 (2008)

  • [96]H. Quentmeier, R. Geffers, E. Jost, R.A.F. Macleod, S. Nagel, S. Röhrs, J. Romani, M. Scherr, M. Zaborski, and H.G. Drexler: SOCS2: inhibitor of JAK2V617F-mediated signal transduction. Leukemia 22, 2169–2175 (2008)

  • [97]S. Barrio, M. Gallardo, E. Albizua, A. Jimenez, I. Rapado, R. Ayala, F. Gilsanz, J.I. Martin-Subero, and J. Martinez-Lopez: Epigenomic profiling in polycythaemia vera and essential thrombocythaemia shows low levels of aberrant DNA methylation. J. Clin. Pathol. 64, 1010–1013 (2011)

  • [98]L. Teofili, M. Martini, T. Cenci, F. Guidi, L. Torti, F. Giona, R. Foà, G. Leone, and L.M. Larocca: Epigenetic alteration of SOCS family members is a possible pathogenetic mechanism in JAK2 wild type myeloproliferative diseases. Int. J. Cancer 123, 1586–1592 (2008)

  • [99]M.Y. Zhang, T.K. Fung, F.Y. Chen, and C.S. Chim: Methylation profiling of SOCS1, SOCS2, SOCS3, CISH and SHP1 in Philadelphia-negative myeloproliferative neoplasm. J. Cell. Mol. Med. 17, 1282–1290 (2013)

  • [100]W. Qin, T. Chen, J.H. Yang, Y. Zhang, R. Xiao, J.T. Lu, T. Wang, M. Zhou, and J.Y. He: Study of single nucleotide polymorphism of SOCS gene in typical myeloproliferative neoplasms. Zhongguo Shi Yan Xue Ye Xue Za Zhi 21, 1507–1512 (2013)

  • [101]A.N. Bullock, J.E. Debreczeni, A.M. Edwards, M. Sundström, and S. Knapp: Crystal structure of the SOCS2-elongin C-elongin B complex defines a prototypical SOCS box ubiquitin ligase. Proc. Natl. Acad. Sci. U. S. A. 103, 7637–7642 (2006)

  • [102]Y.K. Kim, M.J. Kwak, B. Ku, H.Y. Suh, K. Joo, J. Lee, J.U. Jung, and B.H. Oh: Structural basis of intersubunit recognition in elongin BC-cullin 5-SOCS box ubiquitin-protein ligase complexes. Acta Crystallogr. D. Biol. Crystallogr. 69, 1587–1597 (2013)

  • [103]A.N. Bullock, M.C. Rodriguez, J.E. Debreczeni, Z. Songyang, and S. Knapp: Structure of the SOCS4-ElonginB/C complex reveals a distinct SOCS box interface and the molecular basis for SOCS-dependent EGFR degradation. Structure 15, 1493–1504 (2007)

  • [104]S.A. Forbes, G. Bhamra, S. Bamford, E. Dawson, C. Kok, J. Clements, A. Menzies, J.W. Teague, P.A. Futreal, and M.R. Stratton: The Catalogue of Somatic Mutations in Cancer (COSMIC). Curr. Protoc. Hum. Genet. Chapter 10, Unit 10.1.1 (2008)

  • [105]C.E. Stebbins, W.G. Kaelin, and N.P. Pavletich: Structure of the VHL-ElonginC-ElonginB complex: implications for VHL tumor suppressor function. Science 284, 455–461 (1999)

  • [106]K.L. Melmon and S.W. Rosen: Lindau’s disease. Review of the literature and study of a large kindred. Am. J. Med. 36, 595–617 (1964)

  • [107]L. Gossage, T. Eisen, and E.R. Maher: VHL, the story of a tumour suppressor gene. Nat. Rev. Cancer 15, 55–64 (2014)

  • [108]T. Kamura, D.M. Koepp, M.N. Conrad, D. Skowyra, R.J. Moreland, O. Iliopoulos, W.S. Lane, W.G. Kaelin, S.J. Elledge, R.C. Conaway, J.W. Harper, and J.W. Conaway: Rbx1, a component of the VHL tumor suppressor complex and SCF ubiquitin ligase. Science 284, 657–661 (1999)

Article Metrics

  • Information

  • Download

  • Contents

Frontiers in Bioscience-Elite (FBE) is published by IMR Press from Volume 13 Issue 2 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

1 Jan 2016Review

SOCS2: physiological and pathological functions

Elisabeth Letellier 1, Serge Haan 1,*
Affiliation
Article Info

1 Molecular Disease Mechanisms Group, Life Sciences Research Unit, University of Luxembourg, 162A avenue de la Faïencerie, L-1511 Luxembourg, Luxembourg

*Author to whom correspondence should be addressed.

 

Abstract

Suppressors of cytokine signalling (SOCS) proteins are modulators of cytokine and growth factor signalling whose aberrant regulation has been linked to a variety of inflammatory and neoplastic diseases. SOCS proteins are able to act as substrate-recruiting component of E3-ubiquitin ligase complexes and target interacting proteins for degradation. At least some of the family members can also directly inhibit tyrosine kinases such as Janus Kinases (JAK). The most studied family members, CIS, SOCS1, SOCS2 and SOCS3 are important regulators of the JAK-STAT pathway. Here, we focus on SOCS2 and review its biological function as well as its implication in pathological processes. Furthermore, we take advantage of the known crystal structures of SOCS2 to discuss the potential effects of a selection of SOCS2 mutations that were identified in tumour tissues.

Keywords

  • SOCS2
  • GH signalling
  • Cancer
  • CNS
  • Immune Disorders
  • Review

References