SOC1 inhibits HPV-E7-mediated transformation by inducing degradation of E7 protein

Kamio, Masaki; Yoshida, Takafumi; Ogata, Hisanobu; Douchi, Tsutomu; Nagata, Yukihiro; Hasegawa, Mamoru; Yonemitsu, Yoshikazu; Yoshimura, Akihiko

doi:10.1038/sj.onc.1207453

Cited by 65 publications

(46 citation statements)

References 46 publications

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“…Interestingly, the R105E mutant of SOCS1, which disrupts the function of the SH2 domain, still binds Gag (Fig. 2E), indicating that the Gag-SOCS1 association is independent of the tyrosine phosphorylation of Gag, as is the case for both HPV-E7 and Vav (16,17).…”

Section: Socs1mentioning

confidence: 89%

SOCS1 is an inducible host factor during HIV-1 infection and regulates the intracellular trafficking and stability of HIV-1 Gag

Ryo

Tsurutani

Ohba

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Human immunodeficiency virus type 1 (HIV-1) utilizes the macromolecular machinery of the infected host cell to produce progeny virus. The discovery of cellular factors that participate in HIV-1 replication pathways has provided further insight into the molecular basis of virus-host cell interactions. Here, we report that the suppressor of cytokine signaling 1 (SOCS1) is an inducible host factor during HIV-1 infection and regulates the late stages of the HIV-1 replication pathway. SOCS1 can directly bind to the matrix and nucleocapsid regions of the HIV-1 p55 Gag polyprotein and enhance its stability and trafficking, resulting in the efficient production of HIV-1 particles via an IFN signaling-independent mechanism. The depletion of SOCS1 by siRNA reduces both the targeted trafficking and assembly of HIV-1 Gag, resulting in its accumulation as perinuclear solid aggregates that are eventually subjected to lysosomal degradation. These results together indicate that SOCS1 is a crucial host factor that regulates the intracellular dynamism of HIV-1 Gag and could therefore be a potential new therapeutic target for AIDS and its related disorders.AIDS ͉ pathogenesis ͉ drug target ͉ lysozyme

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Section: Socs1mentioning

confidence: 89%

SOCS1 is an inducible host factor during HIV-1 infection and regulates the intracellular trafficking and stability of HIV-1 Gag

Ryo

Tsurutani

Ohba

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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“…MEFs were cultured in DMEM containing 10% FCS (49). MEFs were immortalized by transfection of large T as described (50,51). SOCS3-flox/flox MEFs were then infected with adenovirus carrying Cre recombinase gene (multiplicities of infection of 100; ref.…”

Section: Methodsmentioning

confidence: 99%

Reciprocal Regulation of SOCS 1 and SOCS3 Enhances Resistance to Ionizing Radiation in Glioblastoma Multiforme

Zhou

Miki²,

Eeva³

et al. 2007

Clinical Cancer Research

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Purpose: The expression of suppressors of cytokine signaling 1 (SOCS1) and SOCS3 genes is dysregulated in several solid tumors, causing aberrant activation of cell growth and survival signaling pathways. In this study, we analyzed SOCS1 and SOCS3 gene expression in glioblastoma multiforme (GBM) and studied the role of each protein in GBM cell signaling and radiation resistance. Experimental Design: SOCS1and SOCS3 gene expression was analyzed in 10 GBM cell lines by reverse transcription-PCR and Western blotting. SOCS3 expression was also studied in 12 primary GBM tissues by immunohistochemistry.The methylation status of the SOCS1and SOCS3 loci was determined by methylation-specific PCR. Extracellular signal-regulated kinase (ERK)-mitogen-activated protein kinase (MAPK) activation in GBM cell lines overexpressing SOCS1 or lacking SOCS3 was determined by phosphorylated-specific Western blotting. Radiation responses in SOCS1-positive and SOCS3-deficient GBM cell lines and fibroblasts from wild-type and SOCS1or SOCS3 knockout mice were studied in a clonogenic survival assay.Results: All GBM cell lines tested lacked SOCS1expression, whereas GBM cell lines and primary GBM tumor samples constitutively expressed SOCS3. SOCS1 gene repression was linked to hypermethylation of the SOCS1genetic locus in GBM cells. Reintroduction of SOCS1or blocking SOCS3 expression sensitized cells to radiation and decreased the levels of activated ERK MAPKs in GBM cells. Conclusions: SOCS1and SOCS3 are aberrantly expressed in GBM cell lines and primary tissues. Altered SOCS gene expression leads to increased cell signaling through the ERK-MAPK pathway and may play a role in disease pathogenesis by enhancing GBM radioresistance.

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“…Therefore, SOCS1 and SOCS3 inhibit cytokine signaling by suppressing JAK kinase activity and promoting the degradation of the activated cytokine receptor complex. SOCS1 induction is restricted to interferons and some other cytokines, while SOCS3 is induced by a variety of stimuli, such as interleukins, interferons, and TNFa (Bode et al, 1999;Yasukawa et al, 2003;Kamio et al, 2004). However, since binding of the SH2 domain of SOCS3 is relatively specific to the receptors for STAT3-activating cytokines, such as IL-6, G-CSF, and leptin, the effect of SOCS3 may be relatively restricted to STAT3 (Croker et al, 2003(Croker et al, , 2004Mori et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Loss of SOCS3 in the liver promotes fibrosis by enhancing STAT3-mediated TGF-β1 production

Chinen²,

et al. 2006

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Recently, DNA methylation and reduced expression of the suppressor of the cytokine signaling-3 (SOCS3) gene in human hepatocellular carcinoma (HCC) patients have been reported. However, the roles of SOCS3 in HCC development in vivo have not been clarified. Using RT-PCR analysis and Western blotting, we confirmed that SOCS3 expression was reduced in HCC patients. However, reduced expression of SOCS3 occurred not only in HCC but also in nontumor regions, and this reduction was stronger as the fibrosis grade increased. Furthermore, SOCS3 levels were inversely correlated with signal transducers and activators of transcription-3 (STAT3) activation as well as transforming growth factor (TGF)-b1 levels in the non-HCC region. To define the molecular consequences of SOCS3 silencing/STAT3 hyperactivation and liver fibrosis, we examined liverspecific SOCS3-deficient mice. We demonstrated that SOCS3 deletion in the liver resulted in hyperactivation of STAT3 and promoted ConA-and chemical-induced liver fibrosis. The expression of TGF-b1, a mediator of fibrosis, was enhanced by SOCS3 gene deletion, but suppressed by the overexpression of a dominant-negative STAT3 or SOCS3 both in vivo and in vitro. These data suggest that TGF-b1 is a target gene of STAT3 and could be one of the mechanisms for enhanced fibrosis in SOCS3-deficient mice. Thus, our present study provides a novel role of SOCS3 and STAT3 in HCC development: in addition to the previously characterized oncogenic potentials, STAT3 enhances hepatic fibrosis through the upregulation of TGF-b1 expression, and SOCS3 prevents this process.

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SOC1 inhibits HPV-E7-mediated transformation by inducing degradation of E7 protein

Cited by 65 publications

References 46 publications

SOCS1 is an inducible host factor during HIV-1 infection and regulates the intracellular trafficking and stability of HIV-1 Gag

SOCS1 is an inducible host factor during HIV-1 infection and regulates the intracellular trafficking and stability of HIV-1 Gag

Reciprocal Regulation of SOCS 1 and SOCS3 Enhances Resistance to Ionizing Radiation in Glioblastoma Multiforme

Loss of SOCS3 in the liver promotes fibrosis by enhancing STAT3-mediated TGF-β1 production

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