胞浆
细胞生物学
化学
DNA
生物
生物化学
酶
作者
Ye Cui,Huansha Yu,Xin Zheng,Rui Peng,Qiang Wang,Yi Zhou,Rui Wang,Jiehua Wang,Bo Qu,Nan Shen,Qiang Guo,Xing Liu,Chen Wang
出处
期刊:PLOS Pathogens
[Public Library of Science]
日期:2017-01-17
卷期号:13 (1): e1006156-e1006156
被引量:106
标识
DOI:10.1371/journal.ppat.1006156
摘要
Cyclic GMP-AMP (cGAMP) synthase (cGAS, a.k.a. MB21D1), a cytosolic DNA sensor, catalyzes formation of the second messenger 2'3'-cGAMP that activates the stimulator of interferon genes (STING) signaling. How the cGAS activity is modulated remains largely unknown. Here, we demonstrate that sentrin/SUMO-specific protease 7 (SENP7) interacted with and potentiated cGAS activation. The small ubiquitin-like modifier (SUMO) was conjugated onto the lysine residues 335, 372 and 382 of cGAS, which suppressed its DNA-binding, oligomerization and nucleotidyl-transferase activities. SENP7 reversed this inhibition via catalyzing the cGAS de-SUMOylation. Consistently, silencing of SENP7 markedly impaired the IRF3-responsive gene expression induced by cGAS-STING axis. SENP7-knockdown mice were more susceptible to herpes simplex virus 1 (HSV-1) infection. SENP7 was significantly up-regulated in patients with SLE. Our study highlights the temporal modulation of the cGAS activity via dynamic SUMOylation, uncovering a novel mechanism for fine-tuning the STING signaling in innate immunity.
科研通智能强力驱动
Strongly Powered by AbleSci AI