| First Author | Sun L | Year | 2013 |
| Journal | Science | Volume | 339 |
| Issue | 6121 | Pages | 786-91 |
| PubMed ID | 23258413 | Mgi Jnum | J:196208 |
| Mgi Id | MGI:5487472 | Doi | 10.1126/science.1232458 |
| Citation | Sun L, et al. (2013) Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science 339(6121):786-91 |
| abstractText | 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-beta 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. |
