SENP7 Potentiates CGAS Activation by Relieving SUMO-Mediated Inhibition of Cytosolic DNA Sensing

Overview

Journal PLoS Pathog

Specialty Microbiology

Date 2017 Jan 18

PMID 28095500

Citations 66

Authors

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

Affiliations

Soon will be listed here.

Abstract

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.

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