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Quantitative proteomics and terminomics to elucidate the role of ubiquitination and proteolysis in adaptive immunity
Adaptive immunity is the specialized defence mechanism in vertebrates that evolved to eliminate pathogens. Specialized lymphocytes recognize specific protein epitopes through antigen receptors to mount potent immune responses, many of which are initiated by nuclear factor-kappa B activation and gene...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5031638/ https://www.ncbi.nlm.nih.gov/pubmed/27644975 http://dx.doi.org/10.1098/rsta.2015.0372 |
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author | Klein, Theo Viner, Rosa I. Overall, Christopher M. |
author_facet | Klein, Theo Viner, Rosa I. Overall, Christopher M. |
author_sort | Klein, Theo |
collection | PubMed |
description | Adaptive immunity is the specialized defence mechanism in vertebrates that evolved to eliminate pathogens. Specialized lymphocytes recognize specific protein epitopes through antigen receptors to mount potent immune responses, many of which are initiated by nuclear factor-kappa B activation and gene transcription. Most, if not all, pathways in adaptive immunity are further regulated by post-translational modification (PTM) of signalling proteins, e.g. phosphorylation, citrullination, ubiquitination and proteolytic processing. The importance of PTMs is reflected by genetic or acquired defects in these pathways that lead to a dysfunctional immune response. Here we discuss the state of the art in targeted proteomics and systems biology approaches to dissect the PTM landscape specifically regarding ubiquitination and proteolysis in B- and T-cell activation. Recent advances have occurred in methods for specific enrichment and targeted quantitation. Together with improved instrument sensitivity, these advances enable the accurate analysis of often rare PTM events that are opaque to conventional proteomics approaches, now rendering in-depth analysis and pathway dissection possible. We discuss published approaches, including as a case study the profiling of the N-terminome of lymphocytes of a rare patient with a genetic defect in the paracaspase protease MALT1, a key regulator protease in antigen-driven signalling, which was manifested by elevated linear ubiquitination. This article is part of the themed issue ‘Quantitative mass spectrometry’. |
format | Online Article Text |
id | pubmed-5031638 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The Royal Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-50316382016-10-28 Quantitative proteomics and terminomics to elucidate the role of ubiquitination and proteolysis in adaptive immunity Klein, Theo Viner, Rosa I. Overall, Christopher M. Philos Trans A Math Phys Eng Sci Articles Adaptive immunity is the specialized defence mechanism in vertebrates that evolved to eliminate pathogens. Specialized lymphocytes recognize specific protein epitopes through antigen receptors to mount potent immune responses, many of which are initiated by nuclear factor-kappa B activation and gene transcription. Most, if not all, pathways in adaptive immunity are further regulated by post-translational modification (PTM) of signalling proteins, e.g. phosphorylation, citrullination, ubiquitination and proteolytic processing. The importance of PTMs is reflected by genetic or acquired defects in these pathways that lead to a dysfunctional immune response. Here we discuss the state of the art in targeted proteomics and systems biology approaches to dissect the PTM landscape specifically regarding ubiquitination and proteolysis in B- and T-cell activation. Recent advances have occurred in methods for specific enrichment and targeted quantitation. Together with improved instrument sensitivity, these advances enable the accurate analysis of often rare PTM events that are opaque to conventional proteomics approaches, now rendering in-depth analysis and pathway dissection possible. We discuss published approaches, including as a case study the profiling of the N-terminome of lymphocytes of a rare patient with a genetic defect in the paracaspase protease MALT1, a key regulator protease in antigen-driven signalling, which was manifested by elevated linear ubiquitination. This article is part of the themed issue ‘Quantitative mass spectrometry’. The Royal Society 2016-10-28 /pmc/articles/PMC5031638/ /pubmed/27644975 http://dx.doi.org/10.1098/rsta.2015.0372 Text en © 2016 The Authors. http://creativecommons.org/licenses/by/4.0/ Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited. |
spellingShingle | Articles Klein, Theo Viner, Rosa I. Overall, Christopher M. Quantitative proteomics and terminomics to elucidate the role of ubiquitination and proteolysis in adaptive immunity |
title | Quantitative proteomics and terminomics to elucidate the role of ubiquitination and proteolysis in adaptive immunity |
title_full | Quantitative proteomics and terminomics to elucidate the role of ubiquitination and proteolysis in adaptive immunity |
title_fullStr | Quantitative proteomics and terminomics to elucidate the role of ubiquitination and proteolysis in adaptive immunity |
title_full_unstemmed | Quantitative proteomics and terminomics to elucidate the role of ubiquitination and proteolysis in adaptive immunity |
title_short | Quantitative proteomics and terminomics to elucidate the role of ubiquitination and proteolysis in adaptive immunity |
title_sort | quantitative proteomics and terminomics to elucidate the role of ubiquitination and proteolysis in adaptive immunity |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5031638/ https://www.ncbi.nlm.nih.gov/pubmed/27644975 http://dx.doi.org/10.1098/rsta.2015.0372 |
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