Ray R B, Steele R, Meyer K, Ray R
Division of Infectious Diseases and Immunology, Saint Louis University, MO 63110, USA.
Gene. 1998 Feb 27;208(2):331-6. doi: 10.1016/s0378-1119(98)00030-4.
Hepatitis C virus (HCV) often causes a prolonged and persistent infection, and an association between hepatocellular carcinoma (HCC) and HCV infection has been noted. Recent experimental evidence using a cloned genomic region suggests that the putative core protein of HCV has numerous biological properties and is implicated as a viral factor for HCV mediated pathogenesis. WAF1/Cip1/Sid1 (p21) is the prototype of a family of proteins that inhibit cyclin-dependent kinases (CDK) and regulate cell cycle progression in eukaryotic cells. In this study, we have observed that the HCV core protein represses the transcriptional activity of the p21 promoter when tested separately by an in-vitro transient expression assay using murine fibroblasts (NIH3T3), human hepatocellular carcinoma (HepG2), and human cervical carcinoma (HeLa) cells. A deletion analysis of the p21 promoter suggested that the HCV core responsive region is located downstream of the p53 binding site. A gel mobility shift analysis showed that the HCV core protein does not bind directly to p21 regulatory sequences. Thus, the HCV core protein appears to act as an effector in the promotion of cell growth by repressing p21 transcription through unknown cellular factor(s).
丙型肝炎病毒（HCV）常引起长期持续性感染，且已注意到肝细胞癌（HCC）与HCV感染之间存在关联。最近使用克隆基因组区域的实验证据表明，HCV的推定核心蛋白具有多种生物学特性，并被认为是HCV介导发病机制的病毒因子。WAF1/Cip1/Sid1（p21）是一类抑制细胞周期蛋白依赖性激酶（CDK）并调节真核细胞中细胞周期进程的蛋白质家族的原型。在本研究中，我们观察到，当使用鼠成纤维细胞（NIH3T3）、人肝细胞癌（HepG2）和人宫颈癌（HeLa）细胞通过体外瞬时表达试验单独测试时，HCV核心蛋白会抑制p21启动子的转录活性。对p21启动子的缺失分析表明，HCV核心反应区域位于p53结合位点的下游。凝胶迁移率变动分析表明，HCV核心蛋白不直接结合p21调控序列。因此，HCV核心蛋白似乎通过未知细胞因子抑制p21转录，从而在促进细胞生长中发挥效应器的作用。
