Department of Microbiology, College of Natural Science, Pusan National University, Korea.
Microbiological Resource Research Institute, Pusan National University, Korea.
FEBS Lett. 2022 Oct;596(19):2525-2537. doi: 10.1002/1873-3468.14461. Epub 2022 Aug 8.
The tumour suppressor p53 has been implicated in the host defence system against hepatitis C virus (HCV) infection, although the detailed mechanism remains unknown. Here, we found that p53 inhibits HCV replication by downregulating HCV Core protein levels in human hepatoma cells. For this effect, p53 potentiated the role of E6-associated protein (E6AP) as an E3 ligase to induce ubiquitination and proteasomal degradation of HCV Core. Specifically, p53 facilitated the binding of E6AP to HCV Core through direct interactions with the two proteins. In addition, E6AP failed to induce ubiquitination of HCV Core in the absence of p53, suggesting that p53 increases the E3 ligase activity of E6AP in a triple complex consisting of p53, E6AP and HCV Core.
肿瘤抑制因子 p53 被认为参与了宿主防御系统对丙型肝炎病毒 (HCV) 感染的反应，尽管其详细机制尚不清楚。在这里，我们发现 p53 通过下调人肝癌细胞中的 HCV Core 蛋白水平来抑制 HCV 复制。对于这种作用，p53 增强了 E6 相关蛋白 (E6AP) 作为 E3 连接酶的作用，诱导 HCV Core 的泛素化和蛋白酶体降解。具体而言，p53 通过与这两种蛋白的直接相互作用，促进 E6AP 与 HCV Core 的结合。此外，在没有 p53 的情况下，E6AP 未能诱导 HCV Core 的泛素化，表明 p53 增加了由 p53、E6AP 和 HCV Core 组成的三聚复合物中 E6AP 的 E3 连接酶活性。
