Activation of p53 tumor suppressor by hepatitis C virus core protein
Activation of p53 tumor suppressor by hepatitis C virus core protein
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DOI：
10.1006/viro.1999.9979
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发表时间：
1999-11-10
期刊：
影响因子：
3.7
通讯作者：
Ou, JH
中科院分区：
文献类型：
--
作者：
Lu, W;Lo, SY;Ou, JH
除了作为包装病毒基因组RNA的结构蛋白外，丙型肝炎病毒（HCV）核心蛋白还具有调节功能。在本报告中，我们证明了HCV核心蛋白可以增强肿瘤抑制因子p53的基因转激活活性，无论p53是来自外源基因还是内源基因。HCV核心蛋白能够以p53依赖的方式增强p53下游效应基因p21（waf1/Cip1）的表达，这一观察结果支持了HCV核心蛋白激活p53的观点。进一步的研究表明，HCV核心蛋白也可以通过p53抑制肝细胞的生长。HCV核心蛋白和p53在体外可以相互结合，这一点通过共免疫沉淀、GST pull-down和Far-Western blot检测得到证实。缺失定位分析表明，p53的羧基端序列位于366和380氨基酸之间，是核心蛋白结合所必需的。这些结果提出了HCV核心蛋白可能通过直接物理相互作用激活p53的可能性。慢性感染期间丙型肝炎核心蛋白对p53活性的持续扰动可能对丙型肝炎的发病机制有重要影响。(C) 1999学术出版社。
In addition to being a structural protein that packages the viral genomic RNA, hepatitis C virus (HCV) core protein possesses regulatory functions. In this report, we demonstrate that the HCV core protein could enhance the gene transactivation activity of the tumor suppressor p53, regardless of whether p53 was derived from an exogenous or an endogenous gene. The activation of p53 by the HCV core protein was supported by the observation that the HCV core protein could enhance the expression of p21(waf1/Cip1), a downstream effector gene of p53, in a p53-dependent manner. Further studies indicated that the HCV core protein could also suppress hepatocellular growth via p53. The HCV core protein and p53 could bind to each other in vitro, which was evidenced by the coimmunoprecipitation, the GST pull-down, and the Far-Western blot assays. The deletion-mapping analysis indicated that the carboxy-terminal sequence of p53 located between amino acids 366 and 380 was required for the core protein binding. These results raised the possibility that the HCV core protein might activate p53 through direct physical interaction. The persistent perturbation of p53 activity by the HCV core protein during chronic infection may have important consequences in HCV pathogenesis. (C) 1999 Academic Press.