SOCS regulation of the JAK/STAT signalling pathway

Croker, Ben A.; Kiu, Hiu; Nicholson, Sandra E.

doi:10.1016/j.semcdb.2008.07.010

Cited by 543 publications

(475 citation statements)

References 134 publications

(159 reference statements)

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“…In other studies, however, STAT3 activation is associated with cell cycle arrest [22]. Since SOCS proteins are involved in the regulation of the JAK/STAT pathway [47], we used Western blot to evaluate the effect of SOCS1 on JAK/STAT activation in BLM cells. As indicated for several tumor cell types [48], BLM cells showed constitutively active JAK2/STAT3.…”

Section: Socs1 Expression In Human Melanoma Cells Alters Protein Levementioning

confidence: 98%

Suppressor of cytokine signaling 1 blocks mitosis in human melanoma cells

Parrillas

Martínez-Muñoz

Holgado

et al. 2012

Cell. Mol. Life Sci.

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Hypermethylation of SOCS genes is associated with many human cancers, suggesting a role as tumor suppressors. As adaptor molecules for ubiquitin ligases, SOCS proteins modulate turnover of numerous target proteins. Few SOCS targets identified so far have a direct role in cell cycle progression; the mechanism by which SOCS regulate the cell cycle thus remains largely unknown. Here we show that SOCS1 overexpression inhibits in vitro and in vivo expansion of human melanoma cells, and that SOCS1 associates specifically with Cdh1, triggering its degradation by the proteasome. Cells therefore show a G1/S transition defect, as well as a secondary blockade in mitosis and accumulation of cells in metaphase. SOCS1 expression correlated with a reduction in cyclin D/E levels and an increase in the tumor suppressor p19, as well as the CDK inhibitor p53, explaining the G1/S transition defect. As a result of Cdh1 degradation, SOCS1-expressing cells accumulated cyclin B1 and securin, as well as apparently inactive Cdc20, in mitosis. Levels of the late mitotic Cdh1 substrate Aurora A did not change. These observations comprise a hitherto unreported mechanism of SOCS1 tumor suppression, suggesting this molecule as a candidate for the design of new therapeutic strategies for human melanoma.

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Section: Socs1 Expression In Human Melanoma Cells Alters Protein Levementioning

confidence: 98%

Suppressor of cytokine signaling 1 blocks mitosis in human melanoma cells

Parrillas

Martínez-Muñoz

Holgado

et al. 2012

Cell. Mol. Life Sci.

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“…The SOCS family is composed of eight members: cytokine-inducible Src homology 2 domain-containing protein and SOCS1 to SOCS7 (19,20). SOCS1 plays a key role in the negative regulation of both TLR-mediated signaling and cytokine receptormediated signaling, which are involved in innate immunity and subsequent adaptive immunity (21).…”

mentioning

confidence: 99%

Suppressor of Cytokine Signaling 1 DNA Administration Inhibits Inflammatory and Pathogenic Responses in Autoimmune Myocarditis

Tajiri

Imanaka‐Yoshida

Matsubara

et al. 2012

The Journal of Immunology

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Myocarditis and subsequent dilated cardiomyopathy are major causes of heart failure in young adults. Myocarditis in humans is highly heterogeneous in etiology. Recent studies have indicated that a subgroup of myocarditis patients may benefit from immune-targeted therapies, because autoimmunity plays an important role in myocarditis as well as contributing to the progression to cardiomyopathy and heart failure. Suppressor of cytokine signaling (SOCS) 1 plays a key role in the negative regulation of both TLR- and cytokine receptor-mediated signaling, which is involved in innate immunity and subsequent adaptive immunity. In this study, we investigated the therapeutic effect of SOCS1 DNA administration on experimental autoimmune myocarditis (EAM) in mice. EAM was induced by s.c. immunization with cardiac-specific peptides derived from α myosin H chain in BALB/c mice. In contrast to control myocarditis mice, SOCS1 DNA-injected mice were protected from development of EAM and heart failure. SOCS1 DNA administration was effective for reducing the activation of autoreactive CD4+ T cells by inhibition of the function of Ag-presenting dendritic cells. Our findings suggest that SOCS1 DNA administration has considerable therapeutic potential in individuals with autoimmune myocarditis and dilated cardiomyopathy.

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“…There are four major ways that SOCS proteins inhibit cytokine signaling (51), (i) by blocking STAT recruitment to the cytokine receptor, (ii) by targeting the receptor for degradation by the proteasome, (iii) by binding to JAKs and directly inhibiting their kinase activity, and (iv) by targeting JAKs for degradation by the proteasome. The SOCS family consists of eight members (SOCS1 to SOCS7 and CIS) that contain a conserved SOCS box, a central SH2 domain, and an N terminus of variable length and organization (52)(53)(54). Two of the family members, SOCS1 and SOCS3, contain a kinase inhibitory region (KIR) that serves as a pseudosubstrate for JAKs, blocking JAK kinase activity even in the absence of the SOCS box (55).…”

Section: Discussionmentioning

confidence: 99%

A Suppressor of Cytokine Signaling 1 Antagonist Enhances Antigen-Presenting Capacity and Tumor Cell Antigen-Specific Cytotoxic T Lymphocyte Responses by Human Monocyte-Derived Dendritic Cells

Wang

Yuan

et al. 2013

Clin Vaccine Immunol

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The suppressor of cytokine signaling 1 (SOCS1) has emerged as a critical inhibitory molecule for controlling the cytokine response and antigen presentation by dendritic cells (DCs), thereby regulating the magnitude of both innate and adaptive immunity. The aim of this study was to investigate whether the SOCS1 antagonist pJAK2(1001-1013) peptide can weaken or block the inhibition function of SOCS1 in DCs by evaluating the phenotype and cytokine production, antigen-presenting, and specific Tcell-activating capacities of DCs electroporated with human gastric cancer cell total RNA. Furthermore, STAT1 activation of the JAK/STAT signal pathway mediated by SOCS1 was analyzed by Western blotting. The results demonstrate that the SOCS1 antagonist pJAK2(1001-1013) peptide upregulated the expression of the maturation marker (CD83) and costimulatory molecule (CD86) of RNA-electroporated human monocyte-derived mature DCs (mDCs), potentiated the capacity of mDCs to induce Tcell proliferation, stimulated the secretion of proinflammatory cytokines, and enhanced the cytotoxicity of tumor cell antigenspecific CTLs activated by human gastric cancer cell total RNA-electroporated mDCs. Data from Western blot analysis indicate that STAT1 was further activated in pJAK2(1001-1013) peptide-loaded mDCs. These results imply that the SOCS1 antagonist pJAK2(1001-1013) peptide is an effective reagent for the enhancement of antigen-specific antitumor immunity by DCs.

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SOCS regulation of the JAK/STAT signalling pathway

Cited by 543 publications

References 134 publications

Suppressor of cytokine signaling 1 blocks mitosis in human melanoma cells

Suppressor of cytokine signaling 1 blocks mitosis in human melanoma cells

Suppressor of Cytokine Signaling 1 DNA Administration Inhibits Inflammatory and Pathogenic Responses in Autoimmune Myocarditis

A Suppressor of Cytokine Signaling 1 Antagonist Enhances Antigen-Presenting Capacity and Tumor Cell Antigen-Specific Cytotoxic T Lymphocyte Responses by Human Monocyte-Derived Dendritic Cells

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