Effects of hepatitis B virus X protein on the development of liver cancer.
Hepatitis B virus (HBV) infections play an important role in the development of cirrhosis and hepatocellular carcinoma (HCC). The pathogenesis of HBV-related HCC, however, has not been fully described. Evidence suggests that the HBV X protein (HBx) plays a crucial role in the pathogenesis of HCC. The high occurrence of anti-HBx antibody in the serum of HCC patients indicates that it could be a prognostic marker of HBV infection and HCC. HBx stimulates and influences signal transduction pathways within cells. HBx also binds to such protein targets as p53, proteasome subunits, and UV-damaged DNA binding proteins. It also interacts with the cyclic AMP-responsive element binding protein, ATF-2, NFkappaB, and basal transcription factors. HBx is primarily localized to the cytoplasm, where it interacts with and stimulates protein kinases, including protein kinase C, Janus kinase/STAT, IKK, PI-3-K, stress-activated protein kinase/Jun N-terminal kinase, and protein kinase B/Akt. It is also found in the mitochondrion, where it influences the Bcl-2 family. This review examines the role of HBx in the life cycle of HBV as well as the various signal transduction pathways involved in the pathogenesis of HBV-induced hepatocarcinogenesis.
Zhang
Xiaodong
X
Department of Cancer Research, Institute for Molecular Biology, Nankai University, Tianjin, P. R. China. zhangxd@nankai.edu.cn
Zhang
Hang
H
Ye
Lihong
L
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000821:virology*; D006515:Hepatitis B virus / Q000502:physiology*; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000503:physiopathology; D006801:Humans; D008113:Liver Neoplasms / Q000821:virology*; D015534:Trans-Activators / Q000502:physiology*; D054334:Viral Regulatory and Accessory Proteins
D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein