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.
journal_name
PLoS Pathogjournal_title
PLoS pathogensauthors
Cui Y,Yu H,Zheng X,Peng R,Wang Q,Zhou Y,Wang R,Wang J,Qu B,Shen N,Guo Q,Liu X,Wang Cdoi
10.1371/journal.ppat.1006156subject
Has Abstractpub_date
2017-01-17 00:00:00pages
e1006156issue
1eissn
1553-7366issn
1553-7374pii
PPATHOGENS-D-16-02035journal_volume
13pub_type
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