S6K-STING interaction regulates cytosolic DNA-mediated activation of the transcription factor IRF3.
Nat Immunol
; 17(5): 514-522, 2016 May.
Article
em En
| MEDLINE
| ID: mdl-27043414
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.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
2_ODS3
Base de dados:
MEDLINE
Assunto principal:
DNA
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Proteínas Quinases S6 Ribossômicas 90-kDa
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Fator Regulador 3 de Interferon
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Proteínas de Membrana
Idioma:
En
Revista:
Nat Immunol
Ano de publicação:
2016
Tipo de documento:
Article