期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 284, 期 14, 页码 9237-9246出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M808773200
关键词
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资金
- Cancer Control, Ministry of Health and Welfare [0620100]
- New Drug Target Discovery [M10601000044-06N0100-04410]
- Ministry of Education, Science and Technology, Korea [ROA-2007-000-20051-0]
- Korea Health Promotion Institute [0620100] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [2008-2004100, 2006-02314] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Hepatitis C virus (HCV) infection is often associated with hepatic steatosis and yet the molecular mechanisms of HCV-associated steatosis are poorly understood. Because sterol regulatory element-binding proteins (SREBPs) are the major transcriptional factors in lipogenic gene expression including fatty acid synthase (FAS), we examined the effects of HCV nonstructural proteins on the signaling pathways of SREBP. In this study, we demonstrated that HCV nonstructural 4B (NS4B) protein increased the transcriptional activities of SREBPs. We also showed that HCV NS4B enhanced the protein expression levels of SREBPs and FAS. This was further confirmed in the context of viral RNA replication and HCV infection. The up-regulation of both SREBP and FAS by NS4B protein required phosphatidylinositol 3-kinase activity. We also demonstrated that NS4B protein induced a lipid accumulation in hepatoma cells. In addition, NS4B protein synergistically elevated the transcriptional activity of HCV core-mediated SREBP-1. These results strongly suggest that NS4B may play an important role in HCV-associated liver pathogenesis by modulating the SREBP signaling pathway.
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