A picorna-like virus suppresses the N-end rule pathway to inhibit apoptosis.
A picorna-like virus suppresses the N-end rule pathway to inhibit apoptosis.
复制标题
小RNA样病毒通过抑制N端规则途径来抑制细胞凋亡。
作者：
Wang Z;Xia X;Yang X;Zhang X;Liu Y;Wu D;Fang Y;Liu Y;Xu J;Qiu Y;Zhou X
N-末端规则途径是一种进化上保守的蛋白水解系统，其降解含有称为N-降解决定子的N-末端降解信号的蛋白质，并且已经成为各种过程的关键调节因子。病毒操纵不同的宿主途径以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对N端规则途径有任何影响。在这里，使用小核糖核酸样病毒作为模型，我们发现病毒感染通过诱导N-末端酰胺水解酶1（NTAN 1）的降解促进了caspase切割的果蝇凋亡抑制剂1（DIAP 1）的积累，NTAN 1是一种关键的N-末端规则组分，可识别N-降解决定子以启动该过程。病毒诱导的NTAN 1降解不依赖于多聚泛素化，而依赖于蛋白酶体。此外，病毒诱导的N-末端规则途径抑制抑制细胞凋亡，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-末端规则途径，并揭示了一个新的机制，病毒逃避凋亡。
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 Drosophila 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.