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

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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.

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Authors and Affiliations

  1. Department of Medical Technology, Niigata University Graduate School of Health Sciences, 2-746 Asahimachi-dori, Niigata, 951-8518, Japan

    Yasunobu Matsuda

  2. Department of Gastroenterology, Juntendo University School of Medicine, Juntendo University Hospital of Shizuoka, Shizuoka, Japan

    Takafumi Ichida

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  1. Yasunobu Matsuda
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Correspondence to Yasunobu Matsuda.

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Matsuda, Y., Ichida, T. Impact of hepatitis B virus X protein on the DNA damage response during hepatocarcinogenesis. Med Mol Morphol 42, 138–142 (2009). https://doi.org/10.1007/s00795-009-0457-8

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