Evidence map›Paper›PMID 38863711›Full record

ReviewFrontiers in immunology2024

MALT1 substrate cleavage: what is it good for?

Bahareh Nemati Moud, Franziska Ober, Thomas J O'Neill, Daniel Krappmann

Abstract readReview
In one paragraph

Review in Frontiers in immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing 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

14 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. 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

4 authors.

Bahareh Nemati Moud *Research Unit Signaling and Translation, Group Signaling and Immunity, Molecular Targets and Therapeutics Center, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
Franziska Ober *Research Unit Signaling and Translation, Group Signaling and Immunity, Molecular Targets and Therapeutics Center, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
Thomas J O'NeillResearch Unit Signaling and Translation, Group Signaling and Immunity, Molecular Targets and Therapeutics Center, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
Daniel KrappmannResearch Unit Signaling and Translation, Group Signaling and Immunity, Molecular Targets and Therapeutics Center, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

CARD-BCL10-MALT1 (CBM) signalosomes connect distal signaling of innate and adaptive immune receptors to proximal signaling pathways and immune activation. Four CARD scaffold proteins (CARD9, 10, 11, 14) can form seeds that nucleate the assembly of BCL10-MALT1 filaments in a cell- and stimulus-specific manner. MALT1 (also known as PCASP1) serves a dual function within the assembled CBM complexes. By recruiting TRAF6, MALT1 acts as a molecular scaffold that initiates IκB kinase (IKK)/NF-κB and c-Jun N-terminal kinase (JNK)/AP-1 signaling. In parallel, proximity-induced dimerization of the paracaspase domain activates the MALT1 protease which exerts its function by cleaving a set of specific substrates. While complete MALT1 ablation leads to immune deficiency, selective destruction of either scaffolding or protease function provokes autoimmune inflammation. Thus, balanced MALT1-TRAF6 recruitment and MALT1 substrate cleavage are critical to maintain immune homeostasis and to promote optimal immune activation. Further, MALT1 protease activity drives the survival of aggressive lymphomas and other non-hematologic solid cancers. However, little is known about the relevance of the cleavage of individual substrates for the pathophysiological functions of MALT1. Unbiased serendipity, screening and computational predictions have identified and validated ~20 substrates, indicating that MALT1 targets a quite distinct set of proteins. Known substrates are involved in CBM auto-regulation (MALT1, BCL10 and CARD10), regulation of signaling and adhesion (A20, CYLD, HOIL-1 and Tensin-3), or transcription (RelB) and mRNA stability/translation (Regnase-1, Roquin-1/2 and N4BP1), indicating that MALT1 often targets multiple proteins involved in similar cellular processes. Here, we will summarize what is known about the fate and functions of individual MALT1 substrates and how their cleavage contributes to the biological functions of the MALT1 protease. We will outline what is needed to better connect critical pathophysiological roles of the MALT1 protease with the cleavage of distinct substrates.

Indexed as

Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 ProteinSignal TransductionAnimalsB-Cell CLL-Lymphoma 10 ProteinCARD Signaling Adaptor ProteinsHumansProteolysisSubstrate SpecificityTNF Receptor-Associated Factor 6B-Cell CLL-Lymphoma 10 ProteinCARD Signaling Adaptor ProteinsMALT1 protein, humanMucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 ProteinTNF Receptor-Associated Factor 6API2-MALT1auto-regulationCBM complexcell signalingMALT1proteaseRNA metabolismsubstrate cleavage

Identifiers

PMID38863711
PMCPMC11165066

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.