Activation of the interferon-inducible protein kinase PKR by hepatocellular carcinoma derived-hepatitis C virus core protein.

Abstract

Hepatitis C virus (HCV) is a major etiological agent of chronic liver disease and hepatocellular carcinoma (HCC). We demonstrate herewith that HCV core proteins encoded by sequences isolated from HCC tumor tissues, but not those derived from their non-tumor counterparts in the same liver, co-localise in vitro and in vivo and co-immunoprecipitate with PKR in hepatocytic Huh7 cells. We show that this association in fact augments the autophosphorylation of PKR and the phosphorylation of the translation initiation factor eIF2alpha, which are two markers of PKR activity. The present study therefore identifies a novel model of virus-cell interactions whereby a viral protein, the HCV core, activates PKR activity.

• Authors: N Delhem, A Sabile, R Gajardo, P Podevin, A Abadie, M A Blaton, D Kremsdorf, L Beretta, C Brechot
• Journal: Oncogene (Oncogene) Vol. 20 Issue 41 Pg. 5836-45 (Sep 13 2001) ISSN: 0950-9232 [Print] England
• PMID: 11593389 (Publication Type: Journal Article)

Chemical References

• Neoplasm Proteins
• Viral Core Proteins
• nucleocapsid protein, Hepatitis C virus
• eIF-2 Kinase

Topics

• Amino Acid Sequence
• Apoptosis (physiology)
• Carcinoma, Hepatocellular (metabolism, virology)
• Enzyme Activation
• Hepacivirus (metabolism)
• Humans
• Liver Neoplasms (metabolism, virology)
• Molecular Sequence Data
• Neoplasm Proteins (chemistry, metabolism)
• Phosphorylation
• Sequence Alignment
• Viral Core Proteins (chemistry, metabolism)
• eIF-2 Kinase (metabolism)