@article{625158baf8654114bda2a5710a3f03df,
title = "S6K-STING interaction regulates cytosolic DNA-mediated activation of the transcription factor IRF3",
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.",
author = "Fuan Wang and Tommy Alain and Szretter, {Kristy J.} and Kyle Stephenson and Pol, {Jonathan G.} and Atherton, {Matthew J.} and Hoang, {Huy Dung} and Fonseca, {Bruno D.} and Chadi Zakaria and Lan Chen and Zainab Rangwala and Adam Hesch and Chan, {Eva Sin Yan} and Carly Tuinman and Suthar, {Mehul S.} and Zhaozhao Jiang and Ashkar, {Ali A.} and George Thomas and Kozma, {Sara C.} and Michael Gale and Fitzgerald, {Katherine A.} and Diamond, {Michael S.} and Karen Mossman and Nahum Sonenberg and Yonghong Wan and Lichty, {Brian D.}",
note = "Funding Information: We thank the other members of the McMaster Immunology Research Centre; N. Kazhdan, S. Collins, D. Cummings and C. Shao for technical help; M. Nolland and J. Govero for preparing wild-type and mutant mouse bones; K. McCoy (University of Bern) for Myd88-/-Trif-/-mice; V. Fensterl (Cleveland Clinic) and G. Sen (Cleveland Clinic) for antibody to IFIT3; X. Feng (McMaster University) for Ad-OVA and VV-OVA; M. Orr-Asman (University of Cincinnati) and C. Mercer (University of Cincinnati) for plasmids encoding S6K1; and R. Lin (McGill University) for plasmids encoding TBK1. Supported by the Cancer Research Society/Steven E. Drabin Research Fund (T.A.), Terry Fox Foundation (B.D.L.) and the Canadian Institutes of Health Research (Y.W. and the McMaster Immunology Research Centre). Publisher Copyright: {\textcopyright} 2016 Nature America, Inc. All rights reserved.",
year = "2016",
month = may,
day = "1",
doi = "10.1038/ni.3433",
language = "English",
volume = "17",
pages = "514--522",
journal = "Nature immunology",
issn = "1529-2908",
number = "5",
}