State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.
State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
Elife. 2017 Dec 12;6:e30590. doi: 10.7554/eLife.30590.
The N-end rule pathway is an evolutionarily conserved proteolytic system that degrades proteins containing N-terminal degradation signals called N-degrons, and has emerged as a key regulator of various processes. Viruses manipulate diverse host pathways to facilitate viral replication and evade antiviral defenses. However, it remains unclear if viral infection has any impact on the N-end rule pathway. Here, using a picorna-like virus as a model, we found that viral infection promoted the accumulation of caspase-cleaved inhibitor of apoptosis 1 (DIAP1) by inducing the degradation of N-terminal amidohydrolase 1 (NTAN1), a key N-end rule component that identifies N-degron to initiate the process. The virus-induced NTAN1 degradation is independent of polyubiquitylation but dependent on proteasome. Furthermore, the virus-induced N-end rule pathway suppression inhibits apoptosis and benefits viral replication. Thus, our findings demonstrate that a virus can suppress the N-end rule pathway, and uncover a new mechanism for virus to evade apoptosis.
N 端规则途径是一种进化上保守的蛋白水解系统，可降解含有 N 端降解信号（称为 N 降解物）的蛋白质，已成为各种过程的关键调节剂。病毒通过操纵多种宿主途径来促进病毒复制并逃避抗病毒防御。然而，目前尚不清楚病毒感染是否会对 N 端规则途径产生影响。在这里，我们使用类微小 RNA 病毒作为模型，发现病毒感染通过诱导关键 N 端规则成分 N-末端氨肽酶 1（NTAN1）的降解，促进了半胱天冬酶切割的凋亡抑制因子 1（DIAP1）的积累，NTAN1 是识别 N 降解物以启动该过程的关键 N 端规则成分。病毒诱导的 NTAN1 降解不依赖于多泛素化，但依赖于蛋白酶体。此外，病毒诱导的 N 端规则途径抑制可抑制细胞凋亡并有利于病毒复制。因此，我们的研究结果表明，病毒可以抑制 N 端规则途径，并揭示了病毒逃避细胞凋亡的新机制。
