Cui, YeYu, HuanshaZheng, XinPeng, RuiWang, QiangZhou, YiWang, RuiWang, JiehuaQu, BoShen, NanGuo, QiangLiu, XingWang, Chen2017-03-282017Cui, Y., H. Yu, X. Zheng, R. Peng, Q. Wang, Y. Zhou, R. Wang, et al. 2017. “SENP7 Potentiates cGAS Activation by Relieving SUMO-Mediated Inhibition of Cytosolic DNA Sensing.” PLoS Pathogens 13 (1): e1006156. doi:10.1371/journal.ppat.1006156. http://dx.doi.org/10.1371/journal.ppat.1006156.http://nrs.harvard.edu/urn-3:HUL.InstRepos:31731637Cyclic 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.en-USBiology and life sciencesBiochemistryProteinsPost-translational modificationSUMOylationPrecipitation TechniquesImmunoprecipitationGeneticsGene expressionGene regulationSmall interfering RNAsNucleic acidsRNANon-coding RNAPhysical SciencesChemistryChemical CompoundsOrganic CompoundsAmino AcidsBasic Amino AcidsLysineOrganic ChemistryBiology and Life SciencesImmunologic TechniquesImmunoassaysEnzyme-Linked ImmunoassaysPhysiologyImmune PhysiologyAntibodiesMedicine and Health SciencesImmunologyImmune System ProteinsSpectrum Analysis TechniquesSpectrophotometryFluorophotometryFluorescence Resonance Energy TransferInterferonsJournal Article2017-03-2810.1371/journal.ppat.1006156