Abstract
The HBx protein of hepatitis B virus is involved in deregulation of cell cycle and development of hepatocellular carcinoma. Since c-Myc also plays an important role in cell proliferation and tumor development, we studied its regulation by HBx in a human hepatoma cell line. Co-expression of HBx and c-Myc resulted in increased stability of intracellular c-Myc. HBx blocked the ubiquitination of Myc through a direct interaction with the F box region of Skp2 and destabilization of the SCF(Skp2) complex. We suggest that sustained presence of c-Myc combined with mitogenic activity inherent to HBx may be associated with cell cycle deregulation and transformation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Carcinoma, Hepatocellular
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Cell Cycle / physiology
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Cell Line, Tumor
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Cell Transformation, Neoplastic
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Cysteine Proteinase Inhibitors / metabolism*
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Humans
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Liver Neoplasms
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Proteasome Endopeptidase Complex / metabolism*
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Protein Binding
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Proto-Oncogene Proteins c-myc / metabolism*
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S-Phase Kinase-Associated Proteins / metabolism*
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Trans-Activators / metabolism*
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Ubiquitins / metabolism*
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Viral Regulatory and Accessory Proteins
Substances
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Cysteine Proteinase Inhibitors
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Proto-Oncogene Proteins c-myc
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S-Phase Kinase-Associated Proteins
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Trans-Activators
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Ubiquitins
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Viral Regulatory and Accessory Proteins
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hepatitis B virus X protein
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Proteasome Endopeptidase Complex