Activation of STAT3 by the Hepatitis C Virus Core Protein Leads to Cellular Transformation

DOI PDF 被引用文献16件
  • Takafumi Yoshida
    1Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
  • Toshikatsu Hanada
    1Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
  • Takeshi Tokuhisa
    3Department of Developmental Genetics (H2), Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, Japan
  • Ken-ichiro Kosai
    4Department of Medical Science of Regeneration of the Cardiovascular System, Gifu University School of Medicine, Gifu 500-8705, Japan
  • Michio Sata
    2Second Department of Internal Medicine, Faculty of Medicine, Kurume University, Kurume 830-0011, Japan
  • Michinori Kohara
    5Department of Microbiology and Cell Biology, The Tokyo Metropolitan Institute of Medical Science, Honkomagome, Bunkyo-ku, Tokyo 113, Japan
  • Akihiko Yoshimura
    1Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan

抄録

<jats:p>The signal transducer and activator of transcription (STAT) family proteins are transcription factors critical in mediating cytokine signaling. Among them, STAT3 is often constitutively phosphorylated and activated in human cancers and in transformed cell lines and is implicated in tumorigenesis. However, cause of the persistent activation of STAT3 in human tumor cells is largely unknown. The hepatitis C virus (HCV) is a major etiological agent of non-A and non-B hepatitis, and chronic infection by HCV is associated with development of liver cirrhosis and hepatocellular carcinoma. HCV core protein is proposed to be responsible for the virus-induced transformation. We now report that HCV core protein directly interacts with and activates STAT3 through phosphorylation of the critical tyrosine residue. Activation of STAT3 by the HCV core in NIH-3T3 cells resulted in rapid proliferation and up-regulation of Bcl-XL and cyclin-D1. Additional expression of STAT3 in HCV core-expressing cells resulted in anchorage-independent growth and tumorigenesis. We propose that the HCV core protein cooperates with STAT3, which leads to cellular transformation.</jats:p>

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