Hepatitis C Virus Nonstructural 4B Protein Modulates Sterol Regulatory Element-binding Protein Signaling via the AKT Pathway
| Autor: | Hyun-Jeong Jun, Jae Hun Cheong, Takaji Wakita, Soon B. Hwang, Chul-Yong Park |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Transcriptional Activation
Transcription Genetic viruses Hepacivirus Viral Nonstructural Proteins Biology Biochemistry Mice Cell Line Tumor Animals Humans RNA Messenger Molecular Biology Transcription factor Regulation of gene expression Mechanisms of Signal Transduction virus diseases Cell Biology Lipid Metabolism Molecular biology digestive system diseases Sterol regulatory element-binding protein SREBP signaling pathway Fatty acid synthase Gene Expression Regulation Mutation biology.protein Sterol Regulatory Element Binding Protein 1 lipids (amino acids peptides and proteins) Sterol regulatory element-binding protein 2 Signal transduction Proto-Oncogene Proteins c-akt Signal Transduction Sterol Regulatory Element Binding Protein 2 |
| Zdroj: | Journal of Biological Chemistry. 284:9237-9246 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m808773200 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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