Subcellular localization of HCV core protein regulates its ability for p53 activation and p21 suppression.
Hepatitis C Virus (HCV) is a single stranded RNA virus causing non-A and non-B hepatitis. Core protein is a viral capsid protein that plays an important role in the pathogenesis of HCV. The companion report revealed that an innate form (amino acids [a.a.] 1-191) regulated subcellular localization of a mature form (a.a. 1-173). It was also shown that the innate form in the cytoplasm enhanced the p21 expression and the mature form in the nucleus suppressed the p21 expression. Here we report that the core protein in the cytoplasm increases the amount of p21 via activating p53, and the core protein in the nucleus decreases the amount of p21 by the p53-independent pathway. These observations suggest that the regulation of p21 expression by the core protein via subcellular localization might decide the fate of infected cells either to the proliferation or to the apoptosis.
Yamanaka
Takayuki
T
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
Kodama
Tatsuhiko
T
Doi
Takefumi
T
D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D016174:Hepacivirus / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D011498:Protein Precursors / Q000737:chemistry / Q000378:metabolism; D021381:Protein Transport; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014758:Viral Core Proteins / Q000737:chemistry / Q000378:metabolism*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D011498:Protein Precursors; D016159:Tumor Suppressor Protein p53; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus