Evidence map›Paper›PMID 39145956›Full record

ArticleThe Biochemical journal2024

CARD14 signalosome formation is associated with its endosomal relocation and mTORC1-induced keratinocyte proliferation.

Paul A O'Sullivan, Aigerim Aidarova, Inna S Afonina, Joan Manils, Teresa L M Thurston, Rachael Instrell, Michael Howell, Stefan Boeing, Sashini Ranawana, Melanie B Herpels and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Biochemical journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Review
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

19 authors.

Paul A O'SullivanThe Francis Crick Institute, London NW1 1AT, U.K.
Aigerim AidarovaVIB Center for Inflammation Research and Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
Inna S AfoninaVIB Center for Inflammation Research and Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
Joan ManilsThe Francis Crick Institute, London NW1 1AT, U.K.
Teresa L M ThurstonMRC Centre for Molecular Bacteriology and Infection, Imperial College London, London SW7 2AZ, U.K.
Rachael InstrellThe Francis Crick Institute, London NW1 1AT, U.K.
Michael HowellThe Francis Crick Institute, London NW1 1AT, U.K.
Stefan BoeingThe Francis Crick Institute, London NW1 1AT, U.K.
Sashini RanawanaInstitute of Immunity and Transplantation, University College London, London NW3 2PP, U.K.
Melanie B HerpelsInstitute of Immunity and Transplantation, University College London, London NW3 2PP, U.K.
Riwia ChetianInstitute of Immunity and Transplantation, University College London, London NW3 2PP, U.K.
Matilda BassaInstitute of Immunity and Transplantation, University College London, London NW3 2PP, U.K.
Helen FlynnThe Francis Crick Institute, London NW1 1AT, U.K.
David FrithThe Francis Crick Institute, London NW1 1AT, U.K.
Ambrosius P SnijdersThe Francis Crick Institute, London NW1 1AT, U.K.
Ashleigh HowesNational Heart and Lung Institute, Imperial College London, London W12 0NN, U.K.
Rudi BeyaertVIB Center for Inflammation Research and Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
Anne M BowcockDepartment of Oncological Science, Dermatology, and Genetics and Genome Sciences, Icahn School of Medicine at Mount Sinai, New York 10029, U.S.A.
Steven C LeyInstitute of Immunity and Transplantation, University College London, London NW3 2PP, U.K.ORCID 0000-0001-5911-9223

Funding

Genome-Wide SNP Association in PsoriasisR01AR050266 · NIAMS · WASHINGTON UNIVERSITY · PI BOWCOCK, ANNE MARY · 2007 to 2016
$5.7M
Biotechnology and Biological Sciences Research Council BB/R011834/1NIAMS NIH HHS R01 AR050266
6 · The paper itself

Abstract

Rare mutations in CARD14 promote psoriasis by inducing CARD14-BCL10-MALT1 complexes that activate NF-κB and MAP kinases. Here, the downstream signalling mechanism of the highly penetrant CARD14E138A alteration is described. In addition to BCL10 and MALT1, CARD14E138A associated with several proteins important in innate immune signalling. Interactions with M1-specific ubiquitin E3 ligase HOIP, and K63-specific ubiquitin E3 ligase TRAF6 promoted BCL10 ubiquitination and were essential for NF-κB and MAP kinase activation. In contrast, the ubiquitin binding proteins A20 and ABIN1, both genetically associated with psoriasis development, negatively regulated signalling by inducing CARD14E138A turnover. CARD14E138A localized to early endosomes and was associated with the AP2 adaptor complex. AP2 function was required for CARD14E138A activation of mTOR complex 1 (mTORC1), which stimulated keratinocyte metabolism, but not for NF-κB nor MAP kinase activation. Furthermore, rapamycin ameliorated CARD14E138A-induced keratinocyte proliferation and epidermal acanthosis in mice, suggesting that blocking mTORC1 may be therapeutically beneficial in CARD14-dependent psoriasis.

Indexed as

CARD Signaling Adaptor ProteinsCell ProliferationEndosomesKeratinocytesMechanistic Target of Rapamycin Complex 1Adaptor Proteins, Signal TransducingAnimalsB-Cell CLL-Lymphoma 10 ProteinGuanylate CyclaseGuanylate KinasesHEK293 CellsHumansIntracellular Signaling Peptides and ProteinsMembrane ProteinsMiceNF-kappa BAdaptor Proteins, Signal TransducingB-Cell CLL-Lymphoma 10 ProteinBCL10 protein, humanCARD14 protein, humanCard14 protein, mouseCARD Signaling Adaptor ProteinsGuanylate CyclaseGuanylate KinasesIntracellular Signaling Peptides and ProteinsMechanistic Target of Rapamycin Complex 1Membrane ProteinsNF-kappa BTifab protein, humanTNF Receptor-Associated Factor 6Ubiquitin-Protein Ligasesa20ABIN1CARD14keratinocytesLUBACmTORNF-κBpsoriasis

Identifiers

PMID39145956
PMCPMC11555713

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.