Evidence map›Paper›PMID 27043414›Full record

ArticleNature immunology2016

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

Fuan Wang, Tommy Alain, Kristy J Szretter, Kyle Stephenson, Jonathan G Pol, Matthew J Atherton, Huy-Dung Hoang, Bruno D Fonseca, Chadi Zakaria, Lan Chen and 16 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature immunology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
5.8field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

45 citing papers in PubMed, 82 citations in OpenAlex.

  1. Review
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  9. STING trafficking as a new dimension of immune signaling.The Journal of experimental medicine · 2023
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

26 authors at 10 institutions in 3 countries.

Fuan WangMcMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Tommy AlainChildren's Hospital of Eastern Ontario Research Institute and Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON K1H 8L1, Canada.
Kristy J SzretterDepartment of Medicine, Molecular Microbiology, Pathology & Immunology, Washington, University School of Medicine, St Louis, MO 63110, United States of America.
Kyle StephensonMcMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Jonathan G PolMcMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Matthew J AthertonMcMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Huy-Dung HoangChildren's Hospital of Eastern Ontario Research Institute and Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON K1H 8L1, Canada.
Bruno D FonsecaChildren's Hospital of Eastern Ontario Research Institute and Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON K1H 8L1, Canada.
Chadi ZakariaDepartment of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada.
Lan ChenMcMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Zainab RangwalaMcMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Adam HeschMcMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Eva Sin Yan ChanMcMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Carly TuinmanMcMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Mehul S SutharDepartment of Pediatrics, Emory Vaccine Center, Emory University, Atlanta, GA 30329, United States of America.
Zhaozhao JiangDivision of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, United States of America.
Ali A AshkarMcMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
George ThomasDepartment of of Internal Medicine, Division of Hematology/Oncology, University of Cincinnati Medical School, Cincinnati, 45267-0508 OH, United States of America.
Sara C KozmaDepartment of of Internal Medicine, Division of Hematology/Oncology, University of Cincinnati Medical School, Cincinnati, 45267-0508 OH, United States of America.
Michael GaleDepartment of Immunology, University of Washington School of Medicine, Seattle, Washington, WA98195, United States of America.
Katherine A FitzgeraldDivision of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, United States of America.
Michael S DiamondDepartment of Medicine, Molecular Microbiology, Pathology & Immunology, Washington, University School of Medicine, St Louis, MO 63110, United States of America.
Karen MossmanMcMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Nahum SonenbergDepartment of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada.
Yonghong Wan *McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Brian D Lichty *McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
McMaster University Medical Centre · CAMcMaster University · CAChildren's Hospital of Eastern Ontario · CAMcGill University Health Centre · CAUniversity of Massachusetts Chan Medical School · USWashington University in St. Louis · USEmory University · USInstitut d'Investigació Biomédica de Bellvitge · ESUniversity of Cincinnati · USUniversity of Washington · US

Funding

West Nile Virus and host control of innate defensesU19AI083019 · NIAID · UNIVERSITY OF WASHINGTON · PI GALE, MICHAEL · 2009 to 2018
$22.5M
Innate Immune Control of West Nile VirusR01AI104002 · NIAID · UNIVERSITY OF WASHINGTON · PI DIAMOND, MICHAEL S, GALE, MICHAEL · 2013 to 2017
$3.7M
The Host Response to Hepatitis C VirusR01AI118916 · NIAID · UNIVERSITY OF WASHINGTON · PI GALE, MICHAEL · 2016 to 2020
$2.5M
CIHRNIAID NIH HHS R01 AI104002NIAID NIH HHS R01 AI118916NIAID NIH HHS U19 AI083019
6 · The paper itself

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.

Indexed as

AdenoviridaeAnimalsBone Marrow CellsCells, CulturedCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseCytosolDendritic CellsDNAHEK293 CellsHerpes SimplexHerpesvirus 1, HumanHumansImmunizationImmunoblottingInterferon Regulatory Factor-3Membrane ProteinscGAS protein, mouseCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseDNAInterferon Regulatory Factor-3Irf3 protein, mouseMembrane ProteinsNucleotidyltransferasesOvalbuminProtein Serine-Threonine KinasesRibosomal Protein S6 Kinases, 90-kDaRps6ka1 protein, mouseSting1 protein, mouseSTING ProteinTbk1 protein, mouse

Identifiers

PMID27043414
PMCPMC4917298
OpenAlexW2327960993

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.