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

5-1-2016

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.

Rights and Permissions

Citation: 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

Link to Article in PubMed

Journal/Book/Conference Title

Nature immunology

PubMed ID

27043414