Evidence map›Paper›PMID 27125670›Full record

ArticleGenes & development2016

Mst1 shuts off cytosolic antiviral defense through IRF3 phosphorylation.

Fansen Meng, Ruyuan Zhou, Shiying Wu, Qian Zhang, Qiuheng Jin, Yao Zhou, Steven W Plouffe, Shengduo Liu, Hai Song, Zongping Xia and 6 more

Open access · diamondAbstract read
In one paragraph

Article in Genes & development, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
–field-weighted citation impact
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

56 citing papers in PubMed, 82 citations in OpenAlex.

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  16. Hippo pathway in intestinal diseases: focusing on ferroptosis.Frontiers in cell and developmental biology · 2023
    Review
  17. Article
  18. Article
  19. An overview of the crosstalk between YAP and cGAS-STING signaling in non-small cell lung cancer: it takes two to tango.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022
    Review
  20. Article
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

16 authors at 4 institutions in 2 countries.

Fansen MengLife Sciences Institute, Zhejiang University, Hangzhou 310058, China; Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou 310058, China;
Ruyuan ZhouLife Sciences Institute, Zhejiang University, Hangzhou 310058, China; Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou 310058, China;
Shiying WuLife Sciences Institute, Zhejiang University, Hangzhou 310058, China; Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou 310058, China;
Qian ZhangLife Sciences Institute, Zhejiang University, Hangzhou 310058, China; Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou 310058, China;
Qiuheng JinLife Sciences Institute, Zhejiang University, Hangzhou 310058, China; Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou 310058, China;
Yao ZhouEye Center of the Second Affiliated Hospital School of Medicine, Zhejiang University, Hangzhou 310058, China; Institute of Translational Medicine, Zhejiang University, Hangzhou 310058, China;
Steven W PlouffeDepartment of Pharmacology, Moores Cancer Center, University of California at San Diego, La Jolla, California 92093, USA;
Shengduo LiuLife Sciences Institute, Zhejiang University, Hangzhou 310058, China; Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou 310058, China;
Hai SongLife Sciences Institute, Zhejiang University, Hangzhou 310058, China; Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou 310058, China;
Zongping XiaLife Sciences Institute, Zhejiang University, Hangzhou 310058, China; Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou 310058, China;
Bin ZhaoLife Sciences Institute, Zhejiang University, Hangzhou 310058, China; Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou 310058, China;
Sheng YeLife Sciences Institute, Zhejiang University, Hangzhou 310058, China; Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou 310058, China;
Xin-Hua FengLife Sciences Institute, Zhejiang University, Hangzhou 310058, China; Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou 310058, China; Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Kun-Liang GuanDepartment of Pharmacology, Moores Cancer Center, University of California at San Diego, La Jolla, California 92093, USA;
Jian ZouEye Center of the Second Affiliated Hospital School of Medicine, Zhejiang University, Hangzhou 310058, China; Institute of Translational Medicine, Zhejiang University, Hangzhou 310058, China;
Pinglong XuLife Sciences Institute, Zhejiang University, Hangzhou 310058, China; Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou 310058, China;ORCID 0000-0001-7726-5443
Zhejiang University · CNSecond Affiliated Hospital of Zhejiang University · CNUniversity of California San Diego · USBaylor College of Medicine · US

Funding

GRADUATE TRAINING IN CELLULAR &MOLECULAR PHARMACOLOGYT32GM007752 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BROWN, JOAN HELLER, HANDEL, TRACY M · 1985 to 2023
$13.5M
The mTOR and Hippo pathway in cell growth and cancerR35CA196878 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GUAN, KUN-LIANG · 2015 to 2019
$4.0M
ALK causes TGF-beta insensitivity in lung cancer cellsR21CA209007 · NCI · BAYLOR COLLEGE OF MEDICINE · PI FENG, XIN-HUA · 2016 to 2017
$379k
NCI NIH HHS R21 CA209007NCI NIH HHS R35 CA196878NIGMS NIH HHS T32 GM007752
6 · The paper itself

Abstract

Cytosolic RNA/DNA sensing elicits primary defense against viral pathogens. Interferon regulatory factor 3 (IRF3), a key signal mediator/transcriptional factor of the antiviral-sensing pathway, is indispensible for interferon production and antiviral defense. However, how the status of IRF3 activation is controlled remains elusive. Through a functional screen of the human kinome, we found that mammalian sterile 20-like kinase 1 (Mst1), but not Mst2, profoundly inhibited cytosolic nucleic acid sensing. Mst1 associated with IRF3 and directly phosphorylated IRF3 at Thr75 and Thr253. This Mst1-mediated phosphorylation abolished activated IRF3 homodimerization, its occupancy on chromatin, and subsequent IRF3-mediated transcriptional responses. In addition, Mst1 also impeded virus-induced activation of TANK-binding kinase 1 (TBK1), further attenuating IRF3 activation. As a result, Mst1 depletion or ablation enabled an enhanced antiviral response and defense in cells and mice. Therefore, the identification of Mst1 as a novel physiological negative regulator of IRF3 activation provides mechanistic insights into innate antiviral defense and potential antiviral prevention strategies.

Indexed as

AnimalsCell LineCytosolEnzyme ActivationHEK293 CellsHippo KinasesHumansImmunity, InnateInterferon Regulatory Factor-3MiceMice, Inbred C57BLPhosphorylationProtein BindingProtein Serine-Threonine KinasesRhabdoviridae InfectionsSerine-Threonine Kinase 3Hippo KinasesInterferon Regulatory Factor-3IRF3 protein, humanmammalian sterile 20-like kinase 1, humanProtein Serine-Threonine KinasesSerine-Threonine Kinase 3Stk3 protein, mouseTbk1 protein, mousehost antiviral defenseIRF3Mst1phosphorylationTBK1

Identifiers

PMID27125670
PMCPMC4863739
OpenAlexW2342601652

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

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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.