Crosstalk between the cGAS DNA Sensor and Beclin-1 Autophagy Protein Shapes Innate Antimicrobial Immune Responses

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dc.contributor.authorLiang, Qimingko
dc.contributor.authorSeo, Gil Juko
dc.contributor.authorChoi, Youn Jungko
dc.contributor.authorKwak, Mi Jeongko
dc.contributor.authorGe, Jianningko
dc.contributor.authorRodgers, Mary A.ko
dc.contributor.authorShi, Mudeko
dc.contributor.authorLeslie, Benjamin J.ko
dc.contributor.authorHopfner, Karl-Peterko
dc.contributor.authorHa, Taekjipko
dc.contributor.authorOh, Byung-Hako
dc.contributor.authorJung, Jae U.ko
dc.date.accessioned2014-09-04T08:46:07Z-
dc.date.available2014-09-04T08:46:07Z-
dc.date.created2014-03-25-
dc.date.created2014-03-25-
dc.date.issued2014-02-
dc.identifier.citationCELL HOST & MICROBE, v.15, no.2, pp.228 - 238-
dc.identifier.issn1931-3128-
dc.identifier.urihttp://hdl.handle.net/10203/190181-
dc.description.abstractRobust immune responses are essential for eliminating pathogens but must be metered to avoid prolonged immune activation and potential host damage. Upon recognition of microbial DNA, the cytosolic DNA sensor cyclic GMP-AMP (cGAMP) synthetase (cGAS) produces the second messenger cGAMP to initiate the stimulator of interferon genes (STING) pathway and subsequent interferon (IFN) production. We report that the direct interaction between cGAS and the Beclin-1 autophagy protein not only suppresses cGAMP synthesis to halt IFN production upon double-stranded DNA (dsDNA) stimulation or herpes simplex virus-1 infection, but also enhances autophagy-mediated degradation of cytosolic pathogen DNA to prevent excessive cGAS activation and persistent immune stimulation. Specifically, this interaction releases Rubicon, a negative autophagy regulator, from the Beclin-1 complex, activating phosphatidylinositol 3-kinase class III activity and thereby inducing autophagy to remove cytosolic pathogen DNA. Thus, the cGAS-Beclin-1 interaction shapes innate immune responses by regulating both cGAMP production and autophagy, resulting in well-balanced antimicrobial immune responses.-
dc.languageEnglish-
dc.publisherCELL PRESS-
dc.subjectCYCLIC GMP-AMP-
dc.subjectREGULATORY FACTOR 7-
dc.subjectCYTOSOLIC DNA-
dc.subjectINTRACELLULAR DNA-
dc.subject2ND-MESSENGER-
dc.subjectRUBICON-
dc.subjectPHOSPHORYLATION-
dc.subjectSYNTHASE-
dc.subjectPATHWAY-
dc.subjectATG14L-
dc.titleCrosstalk between the cGAS DNA Sensor and Beclin-1 Autophagy Protein Shapes Innate Antimicrobial Immune Responses-
dc.typeArticle-
dc.identifier.wosid000331475900012-
dc.identifier.scopusid2-s2.0-84893912159-
dc.type.rimsART-
dc.citation.volume15-
dc.citation.issue2-
dc.citation.beginningpage228-
dc.citation.endingpage238-
dc.citation.publicationnameCELL HOST & MICROBE-
dc.identifier.doi10.1016/j.chom.2014.01.009-
dc.embargo.liftdate9999-12-31-
dc.embargo.terms9999-12-31-
dc.contributor.localauthorOh, Byung-Ha-
dc.contributor.nonIdAuthorLiang, Qiming-
dc.contributor.nonIdAuthorSeo, Gil Ju-
dc.contributor.nonIdAuthorChoi, Youn Jung-
dc.contributor.nonIdAuthorGe, Jianning-
dc.contributor.nonIdAuthorRodgers, Mary A.-
dc.contributor.nonIdAuthorShi, Mude-
dc.contributor.nonIdAuthorLeslie, Benjamin J.-
dc.contributor.nonIdAuthorHopfner, Karl-Peter-
dc.contributor.nonIdAuthorHa, Taekjip-
dc.contributor.nonIdAuthorJung, Jae U.-
dc.type.journalArticleArticle-
dc.subject.keywordPlusCYCLIC GMP-AMP-
dc.subject.keywordPlusREGULATORY FACTOR 7-
dc.subject.keywordPlusCYTOSOLIC DNA-
dc.subject.keywordPlusINTRACELLULAR DNA-
dc.subject.keywordPlus2ND-MESSENGER-
dc.subject.keywordPlusRUBICON-
dc.subject.keywordPlusPHOSPHORYLATION-
dc.subject.keywordPlusSYNTHASE-
dc.subject.keywordPlusPATHWAY-
dc.subject.keywordPlusATG14L-
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