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- Title
SENP7 Potentiates cGAS Activation by Relieving SUMO-Mediated Inhibition of Cytosolic DNA Sensing.
- Authors
Cui, Ye; Yu, Huansha; Zheng, Xin; Peng, Rui; Wang, Qiang; Zhou, Yi; Wang, Rui; Wang, Jiehua; Qu, Bo; Shen, Nan; Guo, Qiang; Liu, Xing; Wang, Chen
- 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.
- Subjects
SYNTHASES; PROTEOLYTIC enzymes; OLIGOMERIZATION; NUCLEOTIDYLTRANSFERASES; NATURAL immunity
- Publication
PLoS Pathogens, 2017, Vol 13, Issue 1, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1006156