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

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.

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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Detalhes 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.
Formato:	artículo
Estado:	Versión aceptada para publicación
Fecha de publicación:	2016
País:	España
Recursos:	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
Acesso em linha:	https://hdl.handle.net/2445/126654
Access Level:	acceso abierto
Palavra-chave:	Factors de transcripció Expressió gènica Transcription factors Gene expression

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spelling	S6K-STING interaction regulates cytosolic DNA-mediated activation of the transcription factor IRF3Wang, FuanAlain, TommySzretter, Kristy J.Stephenson, KylePol, Jonathan G.Atherton, Matthew J.Hoang, Huy-DungFonseca, Bruno D.Zakaria, ChadiChen, LanRangwala, ZainabHesch, AdamSin Yan Chan, EvaTuinman, CarlySuthar, Mehul S.Jiang, ZhaozhaoAshkar, Ali A.Thomas, GeorgeKozma, Sara C.Gale, Michael Jr.Fitzgerald, Katherine A.Diamond, Michael S.Mossman, KarenSonenberg, NahumWan, YonghongLichty, Brian D.Factors de transcripcióExpressió gènicaTranscription factorsGene expressionCytosolic 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.Nature Publishing Group2018201820162018info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersion11 p.application/pdfhttps://hdl.handle.net/2445/126654Articles publicats en revistes (Ciències Fisiològiques)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésVersió postprint del document publicat a: https://doi.org/10.1038/ni.3433Nature Immunology, 2016, vol. 17, num. 5, p. 514-522https://doi.org/10.1038/ni.3433(c) Wang et al., 2016info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1266542026-05-29T05:05:01Z
dc.title.none.fl_str_mv	S6K-STING interaction regulates cytosolic DNA-mediated activation of the transcription factor IRF3
title	S6K-STING interaction regulates cytosolic DNA-mediated activation of the transcription factor IRF3
spellingShingle	S6K-STING interaction regulates cytosolic DNA-mediated activation of the transcription factor IRF3 Wang, Fuan Factors de transcripció Expressió gènica Transcription factors Gene expression
title_short	S6K-STING interaction regulates cytosolic DNA-mediated activation of the transcription factor IRF3
title_full	S6K-STING interaction regulates cytosolic DNA-mediated activation of the transcription factor IRF3
title_fullStr	S6K-STING interaction regulates cytosolic DNA-mediated activation of the transcription factor IRF3
title_full_unstemmed	S6K-STING interaction regulates cytosolic DNA-mediated activation of the transcription factor IRF3
title_sort	S6K-STING interaction regulates cytosolic DNA-mediated activation of the transcription factor IRF3
dc.creator.none.fl_str_mv	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.
author	Wang, Fuan
author_facet	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.
author_role	author
author2	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.
author2_role	author author author author author author author author author author author author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	Factors de transcripció Expressió gènica Transcription factors Gene expression
topic	Factors de transcripció Expressió gènica Transcription factors Gene expression
description	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.
publishDate	2016
dc.date.none.fl_str_mv	2016 2018 2018 2018
dc.type.none.fl_str_mv	info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion
format	article
status_str	acceptedVersion
dc.identifier.none.fl_str_mv	https://hdl.handle.net/2445/126654
url	https://hdl.handle.net/2445/126654
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.relation.none.fl_str_mv	Versió postprint del document publicat a: https://doi.org/10.1038/ni.3433 Nature Immunology, 2016, vol. 17, num. 5, p. 514-522 https://doi.org/10.1038/ni.3433
dc.rights.none.fl_str_mv	(c) Wang et al., 2016 info:eu-repo/semantics/openAccess
rights_invalid_str_mv	(c) Wang et al., 2016
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	11 p. application/pdf
dc.publisher.none.fl_str_mv	Nature Publishing Group
publisher.none.fl_str_mv	Nature Publishing Group
dc.source.none.fl_str_mv	Articles publicats en revistes (Ciències Fisiològiques) reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str	Recercat. Dipósit de la Recerca de Catalunya
collection	Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score	15,81155

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

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