| Literature DB >> 27043414 |
Yonghong Wan1,2, Brian D Lichty1,2, Fuan Wang1,2, Tommy Alain3, Kristy J Szretter4, Kyle Stephenson1,2, Jonathan G Pol1,2, Matthew J Atherton1,2, Huy-Dung Hoang3, Bruno D Fonseca3, Chadi Zakaria5, Lan Chen1,2, Zainab Rangwala1,2, Adam Hesch1,2, Eva Sin Yan Chan1,2, Carly Tuinman1,2, Mehul S Suthar6, Zhaozhao Jiang7, Ali A Ashkar1,2, George Thomas8,9,10, Sara C Kozma8,9, Michael Gale11, Katherine A Fitzgerald7, Michael S Diamond4, Karen Mossman1,2, Nahum Sonenberg5.
Abstract
Cytosolic DNA-mediated activation of the transcription factor IRF3 is a key event in host antiviral responses. Here we found that infection with DNA viruses induced interaction of the metabolic checkpoint kinase mTOR downstream effector and kinase S6K1 and the signaling adaptor STING in a manner dependent on the DNA sensor cGAS. We further demonstrated that the kinase domain, but not the kinase function, of S6K1 was required for the S6K1-STING interaction and that the TBK1 critically promoted this process. The formation of a tripartite S6K1-STING-TBK1 complex was necessary for the activation of IRF3, and disruption of this signaling axis impaired the early-phase expression of IRF3 target genes and the induction of T cell responses and mucosal antiviral immunity. Thus, our results have uncovered a fundamental regulatory mechanism for the activation of IRF3 in the cytosolic DNA pathway.Entities:
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Year: 2016 PMID： 27043414 PMCID： PMC4917298 DOI： 10.1038/ni.3433
Source DB: PubMed Journal: Nat Immunol ISSN： 1529-2908 Impact factor: 31.250