Cyclic GMP-AMP Synthase Is a Cytosolic DNA Sensor That Activates the Type I Interferon Pathway
Top Cited Papers
- 15 February 2013
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 339 (6121), 786-791
- https://doi.org/10.1126/science.1232458
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.Keywords
This publication has 22 references indexed in Scilit:
- Coordinated Regulation of Accessory Genetic Elements Produces Cyclic Di-Nucleotides for V. cholerae VirulenceCell, 2012
- Intrinsic antiviral immunityNature Immunology, 2012
- The helicase DDX41 senses intracellular DNA mediated by the adaptor STING in dendritic cellsNature Immunology, 2011
- Innate Immune Recognition of an AT-Rich Stem-Loop DNA Motif in the Plasmodium falciparum GenomeImmunity, 2011
- A diverse range of gene products are effectors of the type I interferon antiviral responseNature, 2011
- Andromeda: A Peptide Search Engine Integrated into the MaxQuant EnvironmentJournal of Proteome Research, 2011
- IFI16 is an innate immune sensor for intracellular DNANature Immunology, 2010
- RNA Polymerase III Detects Cytosolic DNA and Induces Type I Interferons through the RIG-I PathwayCell, 2009
- MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantificationNature Biotechnology, 2008
- DAI (DLM-1/ZBP1) is a cytosolic DNA sensor and an activator of innate immune responseNature, 2007