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Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway.

ABSTRACT: The presence of DNA in the cytoplasm of mammalian cells is a danger signal that triggers host immune responses such as the production of type I interferons. Cytosolic DNA induces interferons through the production of cyclic guanosine monophosphate-adenosine monophosphate (cyclic GMP-AMP, or cGAMP), which binds to and activates the adaptor protein STING. Through biochemical fractionation and quantitative mass spectrometry, we identified a cGAMP synthase (cGAS), which belongs to the nucleotidyltransferase family. Overexpression of cGAS activated the transcription factor IRF3 and induced interferon-? in a STING-dependent manner. Knockdown of cGAS inhibited IRF3 activation and interferon-? induction by DNA transfection or DNA virus infection. cGAS bound to DNA in the cytoplasm and catalyzed cGAMP synthesis. These results indicate that cGAS is a cytosolic DNA sensor that induces interferons by producing the second messenger cGAMP.

SUBMITTER: Sun L

PROVIDER: S-EPMC3863629 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway.

Sun Lijun L Wu Jiaxi J Du Fenghe F Chen Xiang X Chen Zhijian J ZJ

Science (New York, N.Y.) 20121220 6121

The presence of DNA in the cytoplasm of mammalian cells is a danger signal that triggers host immune responses such as the production of type I interferons. Cytosolic DNA induces interferons through the production of cyclic guanosine monophosphate-adenosine monophosphate (cyclic GMP-AMP, or cGAMP), which binds to and activates the adaptor protein STING. Through biochemical fractionation and quantitative mass spectrometry, we identified a cGAMP synthase (cGAS), which belongs to the nucleotidyltra ...[more]

PMID: 23258413

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