Lu R, Misra V
Department of Veterinary Microbiology, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, Saskatchewan S7N 5B4, Canada.
Nucleic Acids Res. 2000 Jun 15;28(12):2446-54. doi: 10.1093/nar/28.12.2446.
Host cell factor (HCF, C1, VCAF or CFF) is a cellular protein that is required for transcription activation of herpes simplex virus (HSV) immediate-early (IE) genes by the virion protein VP16. The biological function of HCF remains unclear. Recently we identified a cellular transcription activator, Luman. As with VP16, the transactivation function of Luman is also regulated by HCF. Here we report a second human protein, Zhangfei (ZF) that interacts with HCF in a fashion similar to Luman and VP16. Although ZF shares no significant sequence homology with Luman, the two proteins have some structural similarities. These include: a basic domain-leucine zipper (bZIP) region, an acidic activation domain and a consensus HCF-binding motif. Unlike Luman, or most other bZIP proteins, ZF by itself did not appear to bind consensus bZIP-binding sites. It was also unable to activate promoters containing these response elements. Although in transient expression assays ectopically expressed ZF was unable to block transactivation by VP16 of a HSV IE promoter, ZF could prevent the expression of several HSV proteins in cells infected with the virus. The ability of ZF to block the synthesis of the HSV IE protein ICP0 relied on its binding to HCF, since a mutant of ZF that was unable to bind HCF was also unable to prevent viral IE protein expression.
宿主细胞因子（HCF，C1、VCAF或CFF）是一种细胞蛋白，病毒体蛋白VP16激活单纯疱疹病毒（HSV）立即早期（IE）基因转录时需要该蛋白。HCF的生物学功能尚不清楚。最近，我们鉴定出一种细胞转录激活因子Luman。与VP16一样，Luman的反式激活功能也受HCF调节。在此，我们报道了另一种人类蛋白张飞（ZF），它以与Luman和VP16相似的方式与HCF相互作用。尽管ZF与Luman没有明显的序列同源性，但这两种蛋白存在一些结构相似性。这些相似性包括：一个碱性结构域-亮氨酸拉链（bZIP）区域、一个酸性激活结构域和一个共有HCF结合基序。与Luman或大多数其他bZIP蛋白不同，ZF自身似乎不结合共有bZIP结合位点。它也无法激活含有这些反应元件的启动子。尽管在瞬时表达试验中，异位表达的ZF无法阻断VP16对HSV IE启动子的反式激活，但ZF可阻止病毒感染细胞中几种HSV蛋白的表达。ZF阻断HSV IE蛋白ICP0合成的能力依赖于其与HCF的结合，因为无法结合HCF的ZF突变体也无法阻止病毒IE蛋白的表达。
