Hepatitis C Virus Core Protein Interacts with 14-3-3 Protein and Activates the Kinase Raf-1

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  • Hiroshi Aoki
    <!--label omitted: 1-->Department of Experimental Pathology, Cancer Institute, Japanese Foundation for Cancer Research, 1-37-1 Kami-Ikebukuro, Toshima-ku, Tokyo 170-8455,1 and
  • Junpei Hayashi
    <!--label omitted: 1-->Department of Experimental Pathology, Cancer Institute, Japanese Foundation for Cancer Research, 1-37-1 Kami-Ikebukuro, Toshima-ku, Tokyo 170-8455,1 and
  • Mitsuhiko Moriyama
    <!--label omitted: 2-->Third Department of Internal Medicine, Nihon University School of Medicine, 30-1, Oyaguchi Kami-machi, Itabashi-ku, Tokyo 173-8610,2 Japan
  • Yasuyuki Arakawa
    <!--label omitted: 2-->Third Department of Internal Medicine, Nihon University School of Medicine, 30-1, Oyaguchi Kami-machi, Itabashi-ku, Tokyo 173-8610,2 Japan
  • Okio Hino
    <!--label omitted: 1-->Department of Experimental Pathology, Cancer Institute, Japanese Foundation for Cancer Research, 1-37-1 Kami-Ikebukuro, Toshima-ku, Tokyo 170-8455,1 and

Abstract

<jats:title>ABSTRACT</jats:title> <jats:p>Persistent hepatitis C virus (HCV) infection is a major cause of chronic liver dysfunction in humans and is epidemiologically closely associated with the development of human hepatocellular carcinoma. Among HCV components, core protein has been reported to be implicated in cell growth regulation both in vitro and in vivo, although mechanisms explaining those effects are still unclear. In the present study, we identified that members of the 14-3-3 protein family associate with HCV core protein. 14-3-3 protein bound to HCV core protein in a phosphoserine-dependent manner. Introduction of HCV core protein caused a substantial increase in Raf-1 kinase activity in HepG2 cells and in a yeast genetic assay. Furthermore, the HCV core–14-3-3 interaction was essential for Raf-1 kinase activation by HCV core protein. These results suggest that HCV core protein may represent a novel type of Raf-1 kinase-activating protein through its interaction with 14-3-3 protein and may contribute to hepatocyte growth regulation.</jats:p>

Journal

  • Journal of Virology

    Journal of Virology 74 (4), 1736-1741, 2000-02-15

    American Society for Microbiology

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