Evidence map›Paper›PMID 24882218›Full record

ArticleImmunity2014

Unanchored K48-linked polyubiquitin synthesized by the E3-ubiquitin ligase TRIM6 stimulates the interferon-IKKε kinase-mediated antiviral response.

Ricardo Rajsbaum, Gijs A Versteeg, Sonja Schmid, Ana M Maestre, Alan Belicha-Villanueva, Carles Martínez-Romero, Jenish R Patel, Juliet Morrison, Giuseppe Pisanelli, Lisa Miorin and 6 more

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In one paragraph

Article in Immunity, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
111citing papers in PubMed, 2 pooled it
6.4field-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

111 citing papers in PubMed, 2 syntheses or guidelines pooled it, 169 citations in OpenAlex.

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51 more citing papers are in PubMed but not listed here.

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 3 countries.

Ricardo RajsbaumDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Gijs A VersteegDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Max F. Perutz Laboratories, University of Vienna, Dr. Bohr-Gasse 9/4, 1030 Vienna, Austria.
Sonja SchmidDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Ana M MaestreDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Alan Belicha-VillanuevaDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Carles Martínez-RomeroDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Jenish R PatelDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Juliet MorrisonDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Giuseppe PisanelliDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Via Federico Delpino 1, 80137 Naples, Italy.
Lisa MiorinDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Maudry Laurent-RolleDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Hong M MoultonDepartment of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331, USA.
David A SteinDepartment of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331, USA.
Ana Fernandez-SesmaDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Benjamin R tenOeverDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Adolfo García-SastreDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Department of Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA. Electronic address: adolfo.garcia-sastre@mssm.edu.
Icahn School of Medicine at Mount Sinai · USOregon State University · USUniversity of Naples Federico II · ITUniversity of Vienna · AT

Funding

Virus CoreU19AI106754 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ALBRECHT, RANDY A. · 2013 to 2017
$26.0M
Molecular Virology and Systems Biology Screening CoreP01AI090935 · NIAID · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI YOUNG, JOHN A T · 2010 to 2014
$20.4M
TRIM mediated host antiviral responses during influenza virus infectionsU19AI083025 · NIAID · UNIVERSITY OF SOUTHERN CALIFORNIA · PI OU, J.-H. JAMES · 2009 to 2013
$10.0M
A Systems-level Approach to Studying HIV/AIDS Susceptibility and Substance AbuseR01DA033773 · NIDA · NORTHWESTERN UNIVERSITY AT CHICAGO · PI WOLINSKY, STEVEN M · 2012 to 2016
$4.6M
MODULATION OF INNATE AND ADAPTIVE IMMUNITY BY DENGUE VIRUSR01AI073450 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI FERNANDEZ-SESMA, ANA · 2008 to 2017
$3.3M
Modulation of the host response to influenza virus infection: The IKKe KinaseR01AI080624 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI TENOEVER, BENJAMIN R. · 2009 to 2013
$2.0M
Role of Mucosal DC Subsets in the Control of Influenza A Virus ImmunityU01AI095611 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI MERAD, MIRIAM, PALUCKA, ANNA KAROLINA · 2011 to 2015
$1.8M
NIAID NIH HHS 1P01AI90935NIAID NIH HHS 1R01AI073450NIAID NIH HHS HHSN266200700010CNIAID NIH HHS HHSN272201000054CNIAID NIH HHS P01 AI090935NIAID NIH HHS P01AI090935NIAID NIH HHS R01 AI073450NIAID NIH HHS R01 AI080624NIAID NIH HHS R01AI080624NIAID NIH HHS U01 AI095611NIAID NIH HHS U01AI095611NIAID NIH HHS U19 AI083025NIAID NIH HHS U19 AI106754NIAID NIH HHS U19AI106754NIDA NIH HHS R01 DA033773
6 · The paper itself

Abstract

Type I interferons (IFN-I) are essential antiviral cytokines produced upon microbial infection. IFN-I elicits this activity through the upregulation of hundreds of IFN-I-stimulated genes (ISGs). The full breadth of ISG induction demands activation of a number of cellular factors including the IκB kinase epsilon (IKKε). However, the mechanism of IKKε activation upon IFN receptor signaling has remained elusive. Here we show that TRIM6, a member of the E3-ubiquitin ligase tripartite motif (TRIM) family of proteins, interacted with IKKε and promoted induction of IKKε-dependent ISGs. TRIM6 and the E2-ubiquitin conjugase UbE2K cooperated in the synthesis of unanchored K48-linked polyubiquitin chains, which activated IKKε for subsequent STAT1 phosphorylation. Our work attributes a previously unrecognized activating role of K48-linked unanchored polyubiquitin chains in kinase activation and identifies the UbE2K-TRIM6-ubiquitin axis as critical for IFN signaling and antiviral response.

Indexed as

AnimalsAntiviral AgentsCells, CulturedEnzyme ActivationHumansI-kappa B KinaseInterferon Type IJanus Kinase 1MicePhosphorylationPolyubiquitinRNA InterferenceRNA, Small InterferingSignal TransductionSTAT1 Transcription FactorTripartite Motif ProteinsAntiviral AgentsI-kappa B KinaseInterferon Type IJAK1 protein, humanJanus Kinase 1PolyubiquitinRNA, Small InterferingSTAT1 protein, humanSTAT1 Transcription FactorTRIM6 protein, humanTripartite Motif ProteinsUBE2K protein, humanUbiquitin-Conjugating EnzymesUbiquitin-Protein Ligases

Identifiers

PMID24882218
PMCPMC4114019
OpenAlexW1998041119

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.