Hepatitis B virus core protein stimulates the proteasome-mediated degradation of viral X protein.
Hepatitis B virus (HBV) X protein (HBx) plays an essential role in viral replication and in the development of hepatocellular carcinoma. HBx has the ability to transactivate the expression of all HBV proteins, including the viral core protein HBc. Consistent with its regulatory role, HBx is relatively unstable and is present at low levels in the cell. We report here that the level of HBx was significantly reduced by the coexpression of HBc in cultured human hepatoma cells, whereas the level of HBx mRNA was unaffected. The repression of HBx by HBc was relieved by treating cells with the proteasome inhibitor MG132, indicating that HBc acts by stimulating the proteasome-mediated degradation of HBx. Moreover, the inhibitory effect of HBc was specific to HBx and did not affect other proteins, including p53, a known target of the proteasome. Although no direct physical interaction between HBc and HBx could be demonstrated, mutational analysis indicated that the C-terminal half of HBc is responsible for its inhibitory effect. These results suggest that HBc functions as a novel regulator of the HBV life cycle and of hepatocellular carcinogenesis through control of the HBx level via an inhibitory feedback type of mechanism.
Kim
Jung-Hwan
JH
School of Life Sciences & Biotechnology, Korea University, Seoul 136-701, Korea.
Kang
Seongman
S
Kim
Joon
J
Ahn
Byung-Yoon
BY
D001483:Base Sequence; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D017931:DNA Primers; D006512:Hepatitis B Core Antigens / Q000378:metabolism / Q000502:physiology*; D006868:Hydrolysis; D009097:Multienzyme Complexes / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins
D017931:DNA Primers; D006512:Hepatitis B Core Antigens; D009097:Multienzyme Complexes; D012333:RNA, Messenger; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex