Hepatitis C virus-core protein facilitates the degradation of Ku70 and reduces DNA-PK activity in hepatocytes.
We have established monoclonal antibodies (MoAbs) that are directed against hepatitis C virus (HCV)-expressing cells. They showed enhanced tumorigenicity after passage in culture for more than 44 days (RzM6-44d cells). To address the mechanism underlying this phenomenon, we characterized the MoAbs, and found that one of the clones recognized a molecule that was down-regulated in the RzM6-44d cells. This molecule was purified and identified as the 70-kDa thyroid autoantigen Ku70. Moreover, expression of the full-length HCV genome or HCV-core protein sequence in WRL68 human embryonic liver cells reduced the level of Ku70 protein, enhanced the ubiquitination of Ku70, and decreased the activity of DNA-activated protein kinase (DNA-PK). Therefore, it appears that the HCV-core protein facilitates the degradation of Ku70 and reduces DNA-PK activity in noncancerous liver cells.
Saitou
Kentarou
K
Department of Biochemistry, School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
Mizumoto
Kiyohisa
K
Nishimura
Tomohiro
T
Kai
Chieko
C
Tsukiyama-Kohara
Kyoko
K
D034961:Antigens, Nuclear / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D051747:DNA-Activated Protein Kinase / Q000037:antagonists & inhibitors*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D016174:Hepacivirus / Q000502:physiology*; D022781:Hepatocytes / Q000821:virology*; D006801:Humans; D000072200:Ku Autoantigen; D008297:Male; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors*; D054875:Ubiquitination; D014758:Viral Core Proteins / Q000502:physiology*
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen