效应器
泛素连接酶
癌症研究
上睑下垂
自噬
内部收益率3
信号转导衔接蛋白
转录因子
作者
Lele Zhang,Ning Wei,Ye Cui,Ze Hong,Xing Liu,Qiang Wang,Senlin Li,Heng Liu,Hua Yu,Yanni Cai,Quanyi Wang,Juanjuan Zhu,Meng Wang,Zhengjun Chen,Chen Wang
出处
期刊:PLOS Pathogens
[Public Library of Science]
日期:2018-11-02
卷期号:14 (11): e1007435-e1007435
被引量:56
标识
DOI:10.1371/journal.ppat.1007435
摘要
Stimulator of interferon genes (STING) is critical for cytosolic DNA-triggered innate immunity. STING is modified by several types of polyubiquitin chains. Here, we report that the deubiquitinase CYLD sustains STING signaling by stabilizing the STING protein. CYLD deficiency promoted the K48-linked polyubiquitination and degradation of STING, attenuating the induction of IRF3-responsive genes after HSV-1 infection or the transfection of DNA ligands. Additionally, CYLD knockout mice were more susceptible to HSV-1 infection than their wild-type (WT) littermates. Mechanistically, STING translocated from the ER to the Golgi upon HSV-1 stimulation; CYLD partially accumulated with STING and interacted selectively with K48-linked polyubiquitin chains on STING, specifically removing the K48-linked polyubiquitin chains from STING and ultimately boosting the innate antiviral response. Our study reveals that CYLD is a novel checkpoint in the cGAS-STING signaling pathway and sheds new light on the dynamic regulation of STING activity by ubiquitination.
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