Hepatitis B virus X protein stimulates the mitochondrial translocation of Raf-1 via oxidative stress.
The human hepatitis B virus (HBV) X protein (HBx) plays a crucial role(s) in the viral life cycle and contributes to the onset of hepatocellular carcinoma (HCC). HBx caused the mitochondrial translocation of Raf-1 kinase either alone or in the context of whole-viral-genome transfections. Mitochondrial translocation of Raf-1 is mediated by HBx-induced oxidative stress and was dependent upon the phosphorylation of Raf-1 at the serine338/339 and Y340/341 residues by p21-activated protein kinase 1 and Src kinase, respectively. These studies provide an insight into the mechanisms by which HBV induces intracellular events relevant to liver disease pathogenesis, including HCC.
Chen
Jun
J
Department of Medicine, SCRB 409, University of California-San Diego, 9500 Gilman Drive, MC0711, La Jolla, CA 92093, USA, and Liver Disease Research Center, Second Xiangya Hospital, Changsha, China.
Siddiqui
Aleem
A
D001692:Biological Transport; D045744:Cell Line, Tumor; D016679:Genome, Viral; D006801:Humans; D008107:Liver Diseases / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021381:Protein Transport; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism*; D012694:Serine / Q000737:chemistry; D015534:Trans-Activators / Q000502:physiology*; D054334:Viral Regulatory and Accessory Proteins; D054462:p21-Activated Kinases; D019061:src-Family Kinases / Q000378:metabolism
D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D012694:Serine; D019061:src-Family Kinases; C515903:PAK1 protein, human; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D054462:p21-Activated Kinases