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BCL10 – Bridging CARDs to Immune Activation
Since the B-cell lymphoma/leukemia 10 (BCL10) protein was first described in 1999, numerous studies have elucidated its key functions in channeling adaptive and innate immune signaling downstream of CARMA/caspase-recruitment domain (CARD) scaffold proteins. While T and B cell antigen receptor (TCR/B...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6039553/ https://www.ncbi.nlm.nih.gov/pubmed/30022982 http://dx.doi.org/10.3389/fimmu.2018.01539 |
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author | Gehring, Torben Seeholzer, Thomas Krappmann, Daniel |
author_facet | Gehring, Torben Seeholzer, Thomas Krappmann, Daniel |
author_sort | Gehring, Torben |
collection | PubMed |
description | Since the B-cell lymphoma/leukemia 10 (BCL10) protein was first described in 1999, numerous studies have elucidated its key functions in channeling adaptive and innate immune signaling downstream of CARMA/caspase-recruitment domain (CARD) scaffold proteins. While T and B cell antigen receptor (TCR/BCR) signaling induces the recruitment of BCL10 bound to mucosa-associated lymphoid tissue (MALT)1 to the lymphocyte-specific CARMA1/CARD11–BCL10–MALT1 (CBM-1) signalosome, alternative CBM complexes utilize different CARMA/CARD scaffolds in distinct innate or inflammatory pathways. BCL10 constitutes the smallest subunit in all CBM signalosomes, containing a 233 amino acid coding for N-terminal CARD as well as a C-terminal Ser/Thr-rich region. BCL10 forms filaments, thereby aggregating into higher-order clusters that mediate and amplify stimulation-induced signals, ultimately leading to MALT1 protease activation and canonical NF-κB and JNK signaling. BCL10 additionally undergoes extensive post-translational regulation involving phosphorylation, ubiquitination, MALT1-catalyzed cleavage, and degradation. Through these feedback and feed-forward events, BCL10 integrates positive and negative regulatory processes that govern the function as well as the dynamic assembly, disassembly, and destruction of CBM complexes. Thus, BCL10 is a critical regulator for activation as well as termination of immune cell signaling, revealing that its role extends far beyond that of a mere linking factor in CBM complexes. |
format | Online Article Text |
id | pubmed-6039553 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-60395532018-07-18 BCL10 – Bridging CARDs to Immune Activation Gehring, Torben Seeholzer, Thomas Krappmann, Daniel Front Immunol Immunology Since the B-cell lymphoma/leukemia 10 (BCL10) protein was first described in 1999, numerous studies have elucidated its key functions in channeling adaptive and innate immune signaling downstream of CARMA/caspase-recruitment domain (CARD) scaffold proteins. While T and B cell antigen receptor (TCR/BCR) signaling induces the recruitment of BCL10 bound to mucosa-associated lymphoid tissue (MALT)1 to the lymphocyte-specific CARMA1/CARD11–BCL10–MALT1 (CBM-1) signalosome, alternative CBM complexes utilize different CARMA/CARD scaffolds in distinct innate or inflammatory pathways. BCL10 constitutes the smallest subunit in all CBM signalosomes, containing a 233 amino acid coding for N-terminal CARD as well as a C-terminal Ser/Thr-rich region. BCL10 forms filaments, thereby aggregating into higher-order clusters that mediate and amplify stimulation-induced signals, ultimately leading to MALT1 protease activation and canonical NF-κB and JNK signaling. BCL10 additionally undergoes extensive post-translational regulation involving phosphorylation, ubiquitination, MALT1-catalyzed cleavage, and degradation. Through these feedback and feed-forward events, BCL10 integrates positive and negative regulatory processes that govern the function as well as the dynamic assembly, disassembly, and destruction of CBM complexes. Thus, BCL10 is a critical regulator for activation as well as termination of immune cell signaling, revealing that its role extends far beyond that of a mere linking factor in CBM complexes. Frontiers Media S.A. 2018-07-04 /pmc/articles/PMC6039553/ /pubmed/30022982 http://dx.doi.org/10.3389/fimmu.2018.01539 Text en Copyright © 2018 Gehring, Seeholzer and Krappmann. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Gehring, Torben Seeholzer, Thomas Krappmann, Daniel BCL10 – Bridging CARDs to Immune Activation |
title | BCL10 – Bridging CARDs to Immune Activation |
title_full | BCL10 – Bridging CARDs to Immune Activation |
title_fullStr | BCL10 – Bridging CARDs to Immune Activation |
title_full_unstemmed | BCL10 – Bridging CARDs to Immune Activation |
title_short | BCL10 – Bridging CARDs to Immune Activation |
title_sort | bcl10 – bridging cards to immune activation |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6039553/ https://www.ncbi.nlm.nih.gov/pubmed/30022982 http://dx.doi.org/10.3389/fimmu.2018.01539 |
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