The X protein of hepatitis B virus binds to the F box protein Skp2 and inhibits the ubiquitination and proteasomal degradation of c-Myc.
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.
Kalra
Neetu
N
Virology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India.
Kumar
Vijay
V
D000818:Animals; D006528:Carcinoma, Hepatocellular; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011485:Protein Binding; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D014452:Ubiquitins / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins
D015853:Cysteine Proteinase Inhibitors; D016271:Proto-Oncogene Proteins c-myc; D044786:S-Phase Kinase-Associated Proteins; D015534:Trans-Activators; D014452:Ubiquitins; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D046988:Proteasome Endopeptidase Complex