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Hepatitis C Virus NS3 Protein Can Activate the Notch-Signaling Pathway through Binding to a Transcription Factor, SRCAP

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Title: Hepatitis C Virus NS3 Protein Can Activate the Notch-Signaling Pathway through Binding to a Transcription Factor, SRCAP
Authors: Iwai, Atsushi Browse this author
Takegami, Tsutomu Browse this author
Shiozaki, Takuya Browse this author
Miyazaki, Tadaaki Browse this author →KAKEN DB
Issue Date: 6-Jun-2011
Publisher: Public Library of Science
Journal Title: PLoS One
Volume: 6
Issue: 6
Start Page: e20718
Publisher DOI: 10.1371/journal.pone.0020718
Abstract: Persistent infections of hepatitis C virus (HCV) are known to be a major risk factor for causing hepatocellular carcinomas. Nonstructural protein 3 (NS3) of HCV has serine protease and RNA helicase domains, and is essential for the viral replication. Further, NS3 is also considered to be involved in the development of HCV-induced hepatocellular carcinomas. In this report, we focus on the function of NS3 protein, and propose a novel possible molecular mechanism which is thought to be related to the tumorigenesis caused by the persistent infection of HCV. We identified SRCAP (Snf2-related CBP activator protein) as a NS3 binding protein using yeast two-hybrid screening, and a co-immunoprecipitation assay demonstrated that NS3 can bind to SRCAP in mammalian cells. The results of a reporter gene assay using Hes-1 promoter which is known to be a target gene activated by Notch, indicate that NS3 and SRCAP cooperatively activate the Hes-1 promoter in Hep3B cells. In addition, we show in this report that also p400, which is known as a protein closely resembling SRCAP, would be targeted by NS3. NS3 exhibited binding activity also to the 1449-1808 region of p400 by a co-immunoprecipitation assay, and further the activation of the Notch-mediated transcription of Hes-1 promoter by NS3 decreased significantly by the combined silencing of SRCAP and p400 mRNA using short hairpin RNA. These results suggest that the HCV NS3 protein is involved in the activation of the Notch-signaling pathway through the targeting to both SRCAP and p400.
Type: article
Appears in Collections:人獣共通感染症国際共同研究所 (International Institute for Zoonosis Control) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 岩井 淳

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