Medical Molecular Morphology

, Volume 42, Issue 3, pp 138–142

Impact of hepatitis B virus X protein on the DNA damage response during hepatocarcinogenesis

Review

Abstract

Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal cancers worldwide. The main HCC-associated diseases are chronic infections with hepatitis B virus (HBV) and hepatitis C virus (HCV), and HBV-associated HCC is still prevalent in Asia. Many studies have suggested that HBV X protein (HBX), which is the most common ORF integrated into the host genome, plays a crucial role in hepatocarcinogenesis. However, the accumulated evidence regarding HBX-mediated signaling pathways is not concordant, and it is difficult to understand the mechanistic nature of HBX-associated hepatocarcinogenesis. For example, HBX was reported to inactivate the early responses to DNA damage via p53-dependent and -independent pathways by interacting with several DNA damage-binding proteins and was also reported to sensitize cells to p53-mediated apoptosis via ataxia-telangiectasia and Rad3-related (ATR)-dependent signaling. HBX also interferes with the centrosome replication process, resulting in rearrangement of chromosomes with micronuclei. Moreover, HBX was found to sensitize protein kinases such as Ras/Raf/mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), stress-activated protein kinase/NH2-terminal-Jun kinase (SAPK/JNK), protein kinase B (PKB/Akt), and Janus kinase/STAT (JAK/STAT), indicating that a variety of signaling pathways may be activated by HBX. In this review, we focus on the roles of HBX in DNA damage repair during HCC development, with a view to achieving a better understanding of the significance of HBX in the early steps of hepatocarcinogenesis.

Key words

Hepatocellular carcinoma Hepatitis B virus HBX DNA damage Ataxia-telangiectasia and Rad3-related (ATR) Centrosome Mitogen-activated protein kinase 

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Copyright information

© The Japanese Society for Clinical Molecular Morphology 2009

Authors and Affiliations

  1. 1.Department of Medical TechnologyNiigata University Graduate School of Health SciencesNiigataJapan
  2. 2.Department of GastroenterologyJuntendo University School of Medicine, Juntendo University Hospital of ShizuokaShizuokaJapan

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