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oai:recercat.cat:2445/1266542025-12-05T09:35:09Zcom_2072_1057col_2072_478799col_2072_478916col_2072_478917

00925njm 22002777a 4500 dc Wang, Fuan author Alain, Tommy author Szretter, Kristy J. author Stephenson, Kyle author Pol, Jonathan G. author Atherton, Matthew J. author Hoang, Huy-Dung author Fonseca, Bruno D. author Zakaria, Chadi author Chen, Lan author Rangwala, Zainab author Hesch, Adam author Sin Yan Chan, Eva author Tuinman, Carly author Suthar, Mehul S. author Jiang, Zhaozhao author Ashkar, Ali A. author Thomas, George author Kozma, Sara C. author Gale, Michael Jr. author Fitzgerald, Katherine A. author Diamond, Michael S. author Mossman, Karen author Sonenberg, Nahum author Wan, Yonghong author Lichty, Brian D. author 2018-11-30T16:02:38Z 2018-11-30T16:02:38Z 2016-04-04 2018-11-30T16:02:38Z 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. Factors de transcripció Expressió gènica Transcription factors Gene expression S6K-STING interaction regulates cytosolic DNA-mediated activation of the transcription factor IRF3