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MALT1 Auto-Proteolysis Is Essential for NF-κB-Dependent Gene Transcription in Activated Lymphocytes

Mucosa-associated lymphoid tissue 1 (MALT1) controls antigen receptor–mediated signalling to nuclear factor κB (NF-κB) through both its adaptor and protease function. Upon antigen stimulation, MALT1 forms a complex with BCL10 and CARMA1, which is essential for initial IκBα phosphorylation and NF-κB...

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Autores principales: Baens, Mathijs, Bonsignore, Luca, Somers, Riet, Vanderheydt, Charlotte, Weeks, Stephen D., Gunnarsson, Jenny, Nilsson, Ewa, Roth, Robert G., Thome, Margot, Marynen, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4126661/
https://www.ncbi.nlm.nih.gov/pubmed/25105596
http://dx.doi.org/10.1371/journal.pone.0103774
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author Baens, Mathijs
Bonsignore, Luca
Somers, Riet
Vanderheydt, Charlotte
Weeks, Stephen D.
Gunnarsson, Jenny
Nilsson, Ewa
Roth, Robert G.
Thome, Margot
Marynen, Peter
author_facet Baens, Mathijs
Bonsignore, Luca
Somers, Riet
Vanderheydt, Charlotte
Weeks, Stephen D.
Gunnarsson, Jenny
Nilsson, Ewa
Roth, Robert G.
Thome, Margot
Marynen, Peter
author_sort Baens, Mathijs
collection PubMed
description Mucosa-associated lymphoid tissue 1 (MALT1) controls antigen receptor–mediated signalling to nuclear factor κB (NF-κB) through both its adaptor and protease function. Upon antigen stimulation, MALT1 forms a complex with BCL10 and CARMA1, which is essential for initial IκBα phosphorylation and NF-κB nuclear translocation. Parallel induction of MALT1 protease activity serves to inactivate negative regulators of NF-κB signalling, such as A20 and RELB. Here we demonstrate a key role for auto-proteolytic MALT1 cleavage in B- and T-cell receptor signalling. MALT1 cleavage occurred after Arginine 149, between the N-terminal death domain and the first immunoglobulin-like region, and did not affect its proteolytic activity. Jurkat T cells expressing an un-cleavable MALT1-R149A mutant showed unaltered initial IκBα phosphorylation and normal nuclear accumulation of NF-κB subunits. Nevertheless, MALT1 cleavage was required for optimal activation of NF-κB reporter genes and expression of the NF-κB targets IL-2 and CSF2. Transcriptome analysis confirmed that MALT1 cleavage after R149 was required to induce NF-κB transcriptional activity in Jurkat T cells. Collectively, these data demonstrate that auto-proteolytic MALT1 cleavage controls antigen receptor-induced expression of NF-κB target genes downstream of nuclear NF-κB accumulation.
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spelling pubmed-41266612014-08-12 MALT1 Auto-Proteolysis Is Essential for NF-κB-Dependent Gene Transcription in Activated Lymphocytes Baens, Mathijs Bonsignore, Luca Somers, Riet Vanderheydt, Charlotte Weeks, Stephen D. Gunnarsson, Jenny Nilsson, Ewa Roth, Robert G. Thome, Margot Marynen, Peter PLoS One Research Article Mucosa-associated lymphoid tissue 1 (MALT1) controls antigen receptor–mediated signalling to nuclear factor κB (NF-κB) through both its adaptor and protease function. Upon antigen stimulation, MALT1 forms a complex with BCL10 and CARMA1, which is essential for initial IκBα phosphorylation and NF-κB nuclear translocation. Parallel induction of MALT1 protease activity serves to inactivate negative regulators of NF-κB signalling, such as A20 and RELB. Here we demonstrate a key role for auto-proteolytic MALT1 cleavage in B- and T-cell receptor signalling. MALT1 cleavage occurred after Arginine 149, between the N-terminal death domain and the first immunoglobulin-like region, and did not affect its proteolytic activity. Jurkat T cells expressing an un-cleavable MALT1-R149A mutant showed unaltered initial IκBα phosphorylation and normal nuclear accumulation of NF-κB subunits. Nevertheless, MALT1 cleavage was required for optimal activation of NF-κB reporter genes and expression of the NF-κB targets IL-2 and CSF2. Transcriptome analysis confirmed that MALT1 cleavage after R149 was required to induce NF-κB transcriptional activity in Jurkat T cells. Collectively, these data demonstrate that auto-proteolytic MALT1 cleavage controls antigen receptor-induced expression of NF-κB target genes downstream of nuclear NF-κB accumulation. Public Library of Science 2014-08-08 /pmc/articles/PMC4126661/ /pubmed/25105596 http://dx.doi.org/10.1371/journal.pone.0103774 Text en © 2014 Baens et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Baens, Mathijs
Bonsignore, Luca
Somers, Riet
Vanderheydt, Charlotte
Weeks, Stephen D.
Gunnarsson, Jenny
Nilsson, Ewa
Roth, Robert G.
Thome, Margot
Marynen, Peter
MALT1 Auto-Proteolysis Is Essential for NF-κB-Dependent Gene Transcription in Activated Lymphocytes
title MALT1 Auto-Proteolysis Is Essential for NF-κB-Dependent Gene Transcription in Activated Lymphocytes
title_full MALT1 Auto-Proteolysis Is Essential for NF-κB-Dependent Gene Transcription in Activated Lymphocytes
title_fullStr MALT1 Auto-Proteolysis Is Essential for NF-κB-Dependent Gene Transcription in Activated Lymphocytes
title_full_unstemmed MALT1 Auto-Proteolysis Is Essential for NF-κB-Dependent Gene Transcription in Activated Lymphocytes
title_short MALT1 Auto-Proteolysis Is Essential for NF-κB-Dependent Gene Transcription in Activated Lymphocytes
title_sort malt1 auto-proteolysis is essential for nf-κb-dependent gene transcription in activated lymphocytes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4126661/
https://www.ncbi.nlm.nih.gov/pubmed/25105596
http://dx.doi.org/10.1371/journal.pone.0103774
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