Cyclic GMP-AMP Synthase Is a Cytosolic DNA Sensor That Activates the Type I Interferon Pathway

被引：3619

作者：

Sun, Lijun ^{[1
,2
]}

Wu, Jiaxi ^{[1
]}

Du, Fenghe ^{[1
,2
]}

Chen, Xiang ^{[1
,2
]}

Chen, Zhijian J. ^{[1
,2
]}

机构：

[1] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA

[2] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA

来源：

SCIENCE | 2013年 / 339卷 / 6121期

关键词：

INTRACELLULAR DNA; INNATE; IDENTIFICATION; IMMUNITY; RANGE; GENE; RNA;

D O I：

10.1126/science.1232458

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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

引用

页码：786 / 791

页数：6

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