title: Mapping of the interacting domains of hepatitis C virus core protein and the double-stranded RNA-activated protein kinase PKR.
abstract: Hepatitis C virus (HCV) core protein has been shown to exhibit several biological properties which suggest an important role in liver pathogenesis and carcinogenesis. During a previous study, we showed that core mutants, isolated from tumour, could directly interact with PKR and maintain it in an activated form. In the present report, we have further investigated this interaction and mapped the core and PKR domains involved. Using glutathion S-transferase fusion protein harbouring the different domains of core or PKR, we determined that the N-terminal 1-58 amino acid (aa) of core protein and the N-terminal 1-180 aa of PKR are responsible for this direct interaction. Using this system we also confirmed that the core-PKR interaction induced PKR autophosphorylation. Furthermore, we found that core protein co-localized and co-immunoprecipitated with PKR in cells expressing a full-length HCV replicon, thus confirming that this interaction occurs when all HCV proteins are expressed. Considering that the activation of PKR has been observed in some cancer cell lines and tissues, it suggests that, depending on the cellular context, PKR may stimulate or inhibit cell proliferation. The precise mapping of core-PKR interaction provides new data to study the molecular mechanism underlying HCV pathogenesis.
authors.affiliation: INSERM, U785, Villejuif, France.
authors.forename: Xue-Bing
authors.initials: XB
authors.lastname: Yan
authors.forename: Serena
authors.initials: S
authors.lastname: Battaglia
authors.forename: Delphine
authors.initials: D
authors.lastname: Boucreux
authors.forename: Zhi
authors.initials: Z
authors.lastname: Chen
authors.forename: Christian
authors.initials: C
authors.lastname: Brechot
authors.forename: Nicole
authors.initials: N
authors.lastname: Pavio
mesh_terms: D016174:Hepacivirus / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D012330:RNA, Double-Stranded / Q000378:metabolism*; D014758:Viral Core Proteins / Q000235:genetics / Q000378:metabolism*; D019892:eIF-2 Kinase / Q000378:metabolism*
chemical_list: D012330:RNA, Double-Stranded; D014758:Viral Core Proteins; D019892:eIF-2 Kinase