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Citrullination in the pathology of inflammatory and autoimmune disorders: recent advances and future perspectives

Numerous post-translational modifications (PTMs) govern the collective metabolism of a cell through altering the structure and functions of proteins. The action of the most prevalent PTMs, encompassing phosphorylation, methylation, acylations, ubiquitination and glycosylation is well documented. A l...

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Autores principales: Ciesielski, Oskar, Biesiekierska, Marta, Panthu, Baptiste, Soszyński, Mirosław, Pirola, Luciano, Balcerczyk, Aneta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8788905/
https://www.ncbi.nlm.nih.gov/pubmed/35079870
http://dx.doi.org/10.1007/s00018-022-04126-3
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author Ciesielski, Oskar
Biesiekierska, Marta
Panthu, Baptiste
Soszyński, Mirosław
Pirola, Luciano
Balcerczyk, Aneta
author_facet Ciesielski, Oskar
Biesiekierska, Marta
Panthu, Baptiste
Soszyński, Mirosław
Pirola, Luciano
Balcerczyk, Aneta
author_sort Ciesielski, Oskar
collection PubMed
description Numerous post-translational modifications (PTMs) govern the collective metabolism of a cell through altering the structure and functions of proteins. The action of the most prevalent PTMs, encompassing phosphorylation, methylation, acylations, ubiquitination and glycosylation is well documented. A less explored protein PTM, conversion of peptidylarginine to citrulline, is the subject of this review. The process of citrullination is catalysed by peptidylarginine deiminases (PADs), a family of conserved enzymes expressed in a variety of human tissues. Accumulating evidence suggest that citrullination plays a significant role in regulating cellular metabolism and gene expression by affecting a multitude of pathways and modulating the chromatin status. Here, we will discuss the biochemical nature of arginine citrullination, the enzymatic machinery behind it and also provide information on the pathological consequences of citrullination in the development of inflammatory diseases (rheumatoid arthritis, multiple sclerosis, psoriasis, systemic lupus erythematosus, periodontitis and COVID-19), cancer and thromboembolism. Finally, developments on inhibitors against protein citrullination and recent clinical trials providing a promising therapeutic approach to inflammatory disease by targeting citrullination are discussed.
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spelling pubmed-87889052022-01-25 Citrullination in the pathology of inflammatory and autoimmune disorders: recent advances and future perspectives Ciesielski, Oskar Biesiekierska, Marta Panthu, Baptiste Soszyński, Mirosław Pirola, Luciano Balcerczyk, Aneta Cell Mol Life Sci Review Numerous post-translational modifications (PTMs) govern the collective metabolism of a cell through altering the structure and functions of proteins. The action of the most prevalent PTMs, encompassing phosphorylation, methylation, acylations, ubiquitination and glycosylation is well documented. A less explored protein PTM, conversion of peptidylarginine to citrulline, is the subject of this review. The process of citrullination is catalysed by peptidylarginine deiminases (PADs), a family of conserved enzymes expressed in a variety of human tissues. Accumulating evidence suggest that citrullination plays a significant role in regulating cellular metabolism and gene expression by affecting a multitude of pathways and modulating the chromatin status. Here, we will discuss the biochemical nature of arginine citrullination, the enzymatic machinery behind it and also provide information on the pathological consequences of citrullination in the development of inflammatory diseases (rheumatoid arthritis, multiple sclerosis, psoriasis, systemic lupus erythematosus, periodontitis and COVID-19), cancer and thromboembolism. Finally, developments on inhibitors against protein citrullination and recent clinical trials providing a promising therapeutic approach to inflammatory disease by targeting citrullination are discussed. Springer International Publishing 2022-01-25 2022 /pmc/articles/PMC8788905/ /pubmed/35079870 http://dx.doi.org/10.1007/s00018-022-04126-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Review
Ciesielski, Oskar
Biesiekierska, Marta
Panthu, Baptiste
Soszyński, Mirosław
Pirola, Luciano
Balcerczyk, Aneta
Citrullination in the pathology of inflammatory and autoimmune disorders: recent advances and future perspectives
title Citrullination in the pathology of inflammatory and autoimmune disorders: recent advances and future perspectives
title_full Citrullination in the pathology of inflammatory and autoimmune disorders: recent advances and future perspectives
title_fullStr Citrullination in the pathology of inflammatory and autoimmune disorders: recent advances and future perspectives
title_full_unstemmed Citrullination in the pathology of inflammatory and autoimmune disorders: recent advances and future perspectives
title_short Citrullination in the pathology of inflammatory and autoimmune disorders: recent advances and future perspectives
title_sort citrullination in the pathology of inflammatory and autoimmune disorders: recent advances and future perspectives
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8788905/
https://www.ncbi.nlm.nih.gov/pubmed/35079870
http://dx.doi.org/10.1007/s00018-022-04126-3
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