Hepatitis B virus, HBx mutants and their role in hepatocellular carcinoma
Hepatitis B virus, HBx mutants and their role in hepatocellular carcinoma
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DOI：
10.3748/wjg.v20.i30.10238
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发表时间：
2014-08-14
影响因子：
4.3
通讯作者：
Qadri, Ishtiaq
中科院分区：
文献类型：
--
作者：
Ali, Ashraf;Abdel-Hafiz, Hany;Qadri, Ishtiaq
肝细胞癌（HCC）是现代世界中由癌症引起的主要死亡原因之一，并且大多数病例与慢性肝炎B病毒（HBV）感染有关。乙型肝炎病毒编码的X蛋白（HBx）在病毒诱导的肝癌的发病机制中起着关键作用。HBx是一种分子量为17 kDa的多功能蛋白，通过与宿主因子的直接或间接相互作用调节多种细胞过程，从而导致HCC。HBX可能干扰氧化应激、DNA修复、信号转导、转录、蛋白质降解、细胞周期进程和凋亡等多种细胞过程。大量研究表明，HBx是最常见的病毒ORF之一，它经常整合到宿主基因组中，其序列变异在HCC中起着至关重要的作用。通过突变或缺失分析表明，HBx的羧基端可能在蛋白质-蛋白质相互作用、转录反式激活、DNA修复、细胞信号传导和HCC发病机制中起作用。迄今为止积累的证据表明，很难理解HBx相关HCC的机制本质，HBx介导的转录反式激活和信号通路可能是一个主要的决定因素。本文讨论了HBx在HCC发展中的作用，特别强调HBx突变体及其推定的靶点。(C)2014百世登出版集团股份有限公司All rights reserved.
Hepatocellular carcinoma (HCC) is one of the leading causes of death induced by cancer in the modern world and majority of the cases are related to chronic hepatitis B virus (HBV) infection. HBV-encoded X protein (HBx) is known to play a pivotal role in the pathogenesis of viral induced HCC. HBx is a multifunctional protein of 17 kDa which modulates several cellular processes by direct or indirect interaction with a repertoire of host factors resulting in HCC. HBX might interfere with several cellular processes such as oxidative stress, DNA repair, signal transduction, transcription, protein degradation, cell cycle progression and apoptosis. A number of reports have indicated that HBx is one of the most common viral ORFs that is often integrated into the host genome and its sequence variants play a crucial role in HCC. By mutational or deletion analysis it was shown that carboxy terminal of HBx has a likely role in protein-protein interactions, transcriptional transactivation, DNA repair, cell, signaling and pathogenesis of HCC. The accumulated evidence thus far suggests that it is difficult to understand the mechanistic nature of HBx associated HCC, and HBx mediated transcriptional transactivation and signaling pathways may be a major determinant. This article addresses the role of HBx in the development of HCC with particular emphasis on HBx mutants and their putative targets. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.