University of Massachusetts Medical School Faculty Publications
Title
S6K-STING interaction regulates cytosolic DNA-mediated activation of the transcription factor IRF3
UMMS Affiliation
Division of Infectious Diseases and Immunology, Department of Medicine
Publication Date
2016-05-01
Document Type
Article
Disciplines
Immunology and Infectious Disease
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.
DOI of Published Version
10.1038/ni.3433
Source
Nat Immunol. 2016 May;17(5):514-22. doi: 10.1038/ni.3433. Epub 2016 Apr 4. Link to article on publisher's site
Related Resources
Journal/Book/Conference Title
Nature immunology
PubMed ID
27043414
Repository Citation
Wang, Fuan; Jiang, Zhaozhao; Fitzgerald, Katherine A.; and Lichty, Brian D., "S6K-STING interaction regulates cytosolic DNA-mediated activation of the transcription factor IRF3" (2016). University of Massachusetts Medical School Faculty Publications. 1126.
https://escholarship.umassmed.edu/faculty_pubs/1126