丙型肝炎病毒核心蛋白诱导的LZIP功能丧失与细胞转化相关。
Hepatitis C virus core protein-induced loss of LZIP function correlates with cellular transformation.
作者信息
Jin D Y, Wang H L, Zhou Y, Chun A C, Kibler K V, Hou Y D, Kung H, Jeang K T
机构信息
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0460, USA.
出版信息
EMBO J. 2000 Feb 15;19(4):729-40. doi: 10.1093/emboj/19.4.729.
Abstract
Hepatitis C virus (HCV) is the major etiological agent of blood-borne non-A non-B hepatitis and a leading cause of liver cirrhosis and hepatocellular carcinoma worldwide. HCV core protein is a multifunctional protein with regulatory functions in cellular transcription and virus-induced transformation and pathogenesis. Here we report on the identification of a bZIP nuclear transcription protein as an HCV core cofactor for transformation. This bZIP factor, designated LZIP, activates CRE-dependent transcription and regulates cell proliferation. Loss of LZIP function in NIH 3T3 cells triggers morphological transformation and anchorage-independent growth. We show that HCV core protein aberrantly sequesters LZIP in the cytoplasm, inactivates LZIP function and potentiates cellular transformation. Our findings suggest that LZIP might serve a novel cellular tumor suppressor function that is targeted by the HCV core.
摘要
丙型肝炎病毒（HCV）是血源性非甲非乙型肝炎的主要病原体，也是全球肝硬化和肝细胞癌的主要病因。HCV核心蛋白是一种多功能蛋白，在细胞转录以及病毒诱导的转化和发病机制中具有调节功能。在此，我们报告鉴定出一种bZIP核转录蛋白作为HCV核心转化辅助因子。这种bZIP因子命名为LZIP，可激活依赖CRE的转录并调节细胞增殖。NIH 3T3细胞中LZIP功能的丧失会引发形态转化和不依赖贴壁的生长。我们发现HCV核心蛋白异常地将LZIP隔离在细胞质中，使LZIP功能失活并增强细胞转化。我们的研究结果表明，LZIP可能具有一种新的细胞肿瘤抑制功能，而HCV核心蛋白可靶向该功能。
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