S6K-STING interaction regulates cytosolic DNA-mediated activation of the transcription factor IRF3

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 dep...

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Detalles Bibliográficos
Autores: Wang, Fuan, Alain, Tommy, Szretter, Kristy J., Stephenson, Kyle, Pol, Jonathan G., Atherton, Matthew J., Hoang, Huy-Dung, Fonseca, Bruno D., Zakaria, Chadi, Chen, Lan, Rangwala, Zainab, Hesch, Adam, Sin Yan Chan, Eva, Tuinman, Carly, Suthar, Mehul S., Jiang, Zhaozhao, Ashkar, Ali A., Thomas, George, Kozma, Sara C., Gale, Michael Jr., Fitzgerald, Katherine A., Diamond, Michael S., Mossman, Karen, Sonenberg, Nahum, Wan, Yonghong, Lichty, Brian D.
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2016
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/126654
Acceso en línea:https://hdl.handle.net/2445/126654
Access Level:acceso abierto
Palabra clave:Factors de transcripció
Expressió gènica
Transcription factors
Gene expression
Descripción
Sumario: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.

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