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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; Chan, Eva Sin Yan; Tuinman, Carly; Suthar, Mehul S; Jiang, Zhaozhao; Ashkar, Ali A; Thomas, George; Kozma, Sara C; Gale, Michael; Fitzgerald, Katherine A; Diamond, Michael S; Mossman, Karen; Sonenberg, Nahum; Wan, Yonghong; Lichty, Brian D.
Afiliação
  • Wang F; McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
  • Alain T; MG DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada.
  • Szretter KJ; Children's Hospital of Eastern Ontario Research Institute and Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON K1H 8L1, Canada.
  • Stephenson K; Department of Medicine, Molecular Microbiology, Pathology & Immunology, Washington, University School of Medicine, St Louis, MO 63110, United States of America.
  • Pol JG; McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
  • Atherton MJ; MG DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada.
  • Hoang HD; McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
  • Fonseca BD; MG DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada.
  • Zakaria C; McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
  • Chen L; MG DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada.
  • Rangwala Z; Children's Hospital of Eastern Ontario Research Institute and Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON K1H 8L1, Canada.
  • Hesch A; Children's Hospital of Eastern Ontario Research Institute and Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON K1H 8L1, Canada.
  • Chan ESY; Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada.
  • Tuinman C; McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
  • Suthar MS; MG DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada.
  • Jiang Z; McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
  • Ashkar AA; MG DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada.
  • Thomas G; McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
  • Kozma SC; MG DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada.
  • Gale M; McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
  • Fitzgerald KA; MG DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada.
  • Diamond MS; McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
  • Mossman K; MG DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada.
  • Sonenberg N; Department of Pediatrics, Emory Vaccine Center, Emory University, Atlanta, GA 30329, United States of America.
  • Wan Y; Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, United States of America.
  • Lichty BD; McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 2_ODS3 Base de dados: MEDLINE Assunto principal: DNA / Proteínas Quinases S6 Ribossômicas 90-kDa / Fator Regulador 3 de Interferon / Proteínas de Membrana Idioma: En Revista: Nat Immunol Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 2_ODS3 Base de dados: MEDLINE Assunto principal: DNA / Proteínas Quinases S6 Ribossômicas 90-kDa / Fator Regulador 3 de Interferon / Proteínas de Membrana Idioma: En Revista: Nat Immunol Ano de publicação: 2016 Tipo de documento: Article