Hepatitis C virus core protein interacts with p53-binding protein, 53BP2/Bbp/ASPP2, and inhibits p53-mediated apoptosis.
The core protein of Hepatitis C virus affects several biological functions of the host cells such as cellular growth and apoptosis. The core was shown to interact with 53BP2/Bbp/ASPP2, a p53-binding protein, in a yeast two-hybrid assay. The core competed with p53 in binding to ASPP2 in vitro. In an apoptosis assay using human osteosarcoma Saos-2 cells or hepatocellular carcinoma HepG2 cells, ectopic expression of p53 induced apoptosis and ASPP2 enhanced this p53-induced apoptosis. However, coexpression of the core with p53 and ASPP2 increased the number of surviving cells. In a reporter assay, neither ASPP2 nor the core with ASPP2 affected the transcriptional activity of p53 on the promoters of Bax and p21, major p53 target genes. These findings suggest that the core inhibits p53-mediated apoptosis by blocking the interaction between p53 and ASPP2, without modulating the transcriptional activity of p53, which plays a role in oncogenesis of hepatocellular carcinoma.
Cao
Yongheng
Y
Department of Biochemistry, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku-gun, Ishikawa 920-0293, Japan.
Hamada
Tomio
T
Matsui
Tadashi
T
Date
Takayasu
T
Iwabuchi
Kuniyoshi
K
D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism; D019085:Fluorescent Antibody Technique, Direct; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D011233:Precipitin Tests; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000502:physiology; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D014758:Viral Core Proteins / Q000235:genetics / Q000378:metabolism*; D015003:Yeasts / Q000235:genetics
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D011994:Recombinant Proteins; C090468:TP53BP2 protein, human; D016159:Tumor Suppressor Protein p53; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D008156:Luciferases