Evidence map›Paper›PMID 28230860›Full record

ArticleCell death & disease2017

CARMA2sh and ULK2 control pathogen-associated molecular patterns recognition in human keratinocytes: psoriasis-linked CARMA2sh mutants escape ULK2 censorship.

Ivan Scudiero, Pellegrino Mazzone, Luca E D'Andrea, Angela Ferravante, Tiziana Zotti, Gianluca Telesio, Gabriele De Rubis, Carla Reale, Maddalena Pizzulo, Shanmugakonar Muralitharan and 2 more

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.6field-weighted citation impact, top 36% 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

7 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. The role of the CBM complex in allergic inflammation and disease.The Journal of allergy and clinical immunology · 2022
    Review
  3. Review
  4. Article
  5. Clinical and Genetic Heterogeneity ofFrontiers in immunology · 2018
    Review
  6. Review
  7. The E3 Ubiquitin Ligase RNF7 Negatively Regulates CARD14/CARMA2sh Signaling.International journal of molecular sciences · 2017
    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

12 authors at 3 institutions in 2 countries.

Ivan ScudieroBiogem, Via Camporeale, Ariano Irpino, Italy.
Pellegrino MazzoneBiogem, Via Camporeale, Ariano Irpino, Italy.
Luca E D'AndreaBiogem, Via Camporeale, Ariano Irpino, Italy.
Angela FerravanteBiogem, Via Camporeale, Ariano Irpino, Italy.
Tiziana ZottiGenus Biotechnology, Universita' del Sannio, Via Port'Arsa 10, Benevento, Italy.
Gianluca TelesioBiogem, Via Camporeale, Ariano Irpino, Italy.
Gabriele De RubisBiogem, Via Camporeale, Ariano Irpino, Italy.
Carla RealeBiogem, Via Camporeale, Ariano Irpino, Italy.
Maddalena PizzuloBiogem, Via Camporeale, Ariano Irpino, Italy.
Shanmugakonar MuralitharanLaboratory Animal Research Centre, Qatar University, PO Box 2713, Doha, Qatar.
Pasquale VitoBiogem, Via Camporeale, Ariano Irpino, Italy.
Romania StiloBiogem, Via Camporeale, Ariano Irpino, Italy.
Biogem · ITQatar University · QAUniversity of Sannio · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The molecular complexes formed by specific members of the family of CARMA proteins, the CARD domain-containing adapter molecule BCL10 and MALT1 (CBM complex) represent a central hub in regulating activation of the pleiotropic transcription factor NF-κB. Recently, missense mutations in CARMA2sh have been shown to cause psoriasis in a dominant manner and with high penetrancy. Here, we demonstrate that in human keratinocytes CARMA2sh plays an essential role in the signal transduction pathway that connects pathogen-associated molecular patterns recognition to NF-κB activation. We also find that the serine/threonine kinase ULK2 binds to and phosphorylates CARMA2sh, thereby inhibiting its capacity to activate NF-κB by promoting lysosomal degradation of BCL10, which is essential for CARMA2sh-mediated NF-κB signaling. Remarkably, CARMA2sh mutants associated with psoriasis escape ULK2 inhibition. Finally, we show that a peptide blocking CARD-mediated BCL10 interactions reduces the capacity of psoriasis-linked CARMA2sh mutants to activate NF-κB. Our work elucidates a fundamental signaling mechanism operating in human keratinocytes and opens to novel potential tools for the therapeutical treatment of human skin disorders.

Indexed as

Adaptor Proteins, Signal TransducingB-Cell CLL-Lymphoma 10 ProteinCARD Signaling Adaptor ProteinsCell LineGuanylate CyclaseHEK293 CellsHumansKeratinocytesMembrane ProteinsNF-kappa BPathogen-Associated Molecular Pattern MoleculesPhosphorylationProtein BindingProtein Serine-Threonine KinasesPsoriasisSignal TransductionAdaptor Proteins, Signal TransducingB-Cell CLL-Lymphoma 10 ProteinBCL10 protein, humanCARD14 protein, humanCARD Signaling Adaptor ProteinsGuanylate CyclaseMembrane ProteinsNF-kappa BPathogen-Associated Molecular Pattern MoleculesProtein Serine-Threonine KinasesUlk2 protein, human

Identifiers

PMID28230860
PMCPMC5386493
OpenAlexW2590785943

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.