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The paracaspase MALT1 cleaves HOIL1 reducing linear ubiquitination by LUBAC to dampen lymphocyte NF-κB signalling
Antigen receptor signalling activates the canonical NF-κB pathway via the CARD11/BCL10/MALT1 (CBM) signalosome involving key, yet ill-defined roles for linear ubiquitination. The paracaspase MALT1 cleaves and removes negative checkpoint proteins, amplifying lymphocyte responses in NF-κB activation a...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Pub. Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4659944/ https://www.ncbi.nlm.nih.gov/pubmed/26525107 http://dx.doi.org/10.1038/ncomms9777 |
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author | Klein, Theo Fung, Shan-Yu Renner, Florian Blank, Michael A. Dufour, Antoine Kang, Sohyeong Bolger-Munro, Madison Scurll, Joshua M. Priatel, John J. Schweigler, Patrick Melkko, Samu Gold, Michael R. Viner, Rosa I. Régnier, Catherine H. Turvey, Stuart E. Overall, Christopher M. |
author_facet | Klein, Theo Fung, Shan-Yu Renner, Florian Blank, Michael A. Dufour, Antoine Kang, Sohyeong Bolger-Munro, Madison Scurll, Joshua M. Priatel, John J. Schweigler, Patrick Melkko, Samu Gold, Michael R. Viner, Rosa I. Régnier, Catherine H. Turvey, Stuart E. Overall, Christopher M. |
author_sort | Klein, Theo |
collection | PubMed |
description | Antigen receptor signalling activates the canonical NF-κB pathway via the CARD11/BCL10/MALT1 (CBM) signalosome involving key, yet ill-defined roles for linear ubiquitination. The paracaspase MALT1 cleaves and removes negative checkpoint proteins, amplifying lymphocyte responses in NF-κB activation and in B-cell lymphoma subtypes. To identify new human MALT1 substrates, we compare B cells from the only known living MALT1(mut/mut) patient with healthy MALT1(+/mut) family members using 10-plex Tandem Mass Tag TAILS N-terminal peptide proteomics. We identify HOIL1 of the linear ubiquitin chain assembly complex as a novel MALT1 substrate. We show linear ubiquitination at B-cell receptor microclusters and signalosomes. Late in the NF-κB activation cycle HOIL1 cleavage transiently reduces linear ubiquitination, including of NEMO and RIP1, dampening NF-κB activation and preventing reactivation. By regulating linear ubiquitination, MALT1 is both a positive and negative pleiotropic regulator of the human canonical NF-κB pathway—first promoting activation via the CBM—then triggering HOIL1-dependent negative-feedback termination, preventing reactivation. |
format | Online Article Text |
id | pubmed-4659944 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Pub. Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-46599442015-12-04 The paracaspase MALT1 cleaves HOIL1 reducing linear ubiquitination by LUBAC to dampen lymphocyte NF-κB signalling Klein, Theo Fung, Shan-Yu Renner, Florian Blank, Michael A. Dufour, Antoine Kang, Sohyeong Bolger-Munro, Madison Scurll, Joshua M. Priatel, John J. Schweigler, Patrick Melkko, Samu Gold, Michael R. Viner, Rosa I. Régnier, Catherine H. Turvey, Stuart E. Overall, Christopher M. Nat Commun Article Antigen receptor signalling activates the canonical NF-κB pathway via the CARD11/BCL10/MALT1 (CBM) signalosome involving key, yet ill-defined roles for linear ubiquitination. The paracaspase MALT1 cleaves and removes negative checkpoint proteins, amplifying lymphocyte responses in NF-κB activation and in B-cell lymphoma subtypes. To identify new human MALT1 substrates, we compare B cells from the only known living MALT1(mut/mut) patient with healthy MALT1(+/mut) family members using 10-plex Tandem Mass Tag TAILS N-terminal peptide proteomics. We identify HOIL1 of the linear ubiquitin chain assembly complex as a novel MALT1 substrate. We show linear ubiquitination at B-cell receptor microclusters and signalosomes. Late in the NF-κB activation cycle HOIL1 cleavage transiently reduces linear ubiquitination, including of NEMO and RIP1, dampening NF-κB activation and preventing reactivation. By regulating linear ubiquitination, MALT1 is both a positive and negative pleiotropic regulator of the human canonical NF-κB pathway—first promoting activation via the CBM—then triggering HOIL1-dependent negative-feedback termination, preventing reactivation. Nature Pub. Group 2015-11-03 /pmc/articles/PMC4659944/ /pubmed/26525107 http://dx.doi.org/10.1038/ncomms9777 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Klein, Theo Fung, Shan-Yu Renner, Florian Blank, Michael A. Dufour, Antoine Kang, Sohyeong Bolger-Munro, Madison Scurll, Joshua M. Priatel, John J. Schweigler, Patrick Melkko, Samu Gold, Michael R. Viner, Rosa I. Régnier, Catherine H. Turvey, Stuart E. Overall, Christopher M. The paracaspase MALT1 cleaves HOIL1 reducing linear ubiquitination by LUBAC to dampen lymphocyte NF-κB signalling |
title | The paracaspase MALT1 cleaves HOIL1 reducing linear ubiquitination by LUBAC to dampen lymphocyte NF-κB signalling |
title_full | The paracaspase MALT1 cleaves HOIL1 reducing linear ubiquitination by LUBAC to dampen lymphocyte NF-κB signalling |
title_fullStr | The paracaspase MALT1 cleaves HOIL1 reducing linear ubiquitination by LUBAC to dampen lymphocyte NF-κB signalling |
title_full_unstemmed | The paracaspase MALT1 cleaves HOIL1 reducing linear ubiquitination by LUBAC to dampen lymphocyte NF-κB signalling |
title_short | The paracaspase MALT1 cleaves HOIL1 reducing linear ubiquitination by LUBAC to dampen lymphocyte NF-κB signalling |
title_sort | paracaspase malt1 cleaves hoil1 reducing linear ubiquitination by lubac to dampen lymphocyte nf-κb signalling |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4659944/ https://www.ncbi.nlm.nih.gov/pubmed/26525107 http://dx.doi.org/10.1038/ncomms9777 |
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