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

Lijun Sun, Jiaxi Wu, Fenghe Du, Xiang Chen, Zhijian J. Chen

Research output: Contribution to journalArticle

1179 Citations (Scopus)

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-β in a STING-dependent manner. Knockdown of cGAS inhibited IRF3 activation and interferon-β 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.

Original languageEnglish (US)
Pages (from-to)786-791
Number of pages6
JournalScience
Volume339
Issue number6121
DOIs
StatePublished - Feb 15 2013

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GMP synthase (glutamine-hydrolyzing)
Interferon Type I
DNA
Interferons
DNA Virus Infections
Cytoplasm
Nucleotidyltransferases
cyclic guanosine monophosphate-adenosine monophosphate

ASJC Scopus subject areas

  • General

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Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. / Sun, Lijun; Wu, Jiaxi; Du, Fenghe; Chen, Xiang; Chen, Zhijian J.

In: Science, Vol. 339, No. 6121, 15.02.2013, p. 786-791.

Research output: Contribution to journalArticle

Sun, Lijun ; Wu, Jiaxi ; Du, Fenghe ; Chen, Xiang ; Chen, Zhijian J. / Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. In: Science. 2013 ; Vol. 339, No. 6121. pp. 786-791.
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