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Chemical ubiquitination for decrypting a cellular code
The modification of proteins with ubiquitin (Ub) is an important regulator of eukaryotic biology and deleterious perturbation of this process is widely linked to the onset of various diseases. The regulatory capacity of the Ub signal is high and, in part, arises from the capability of Ub to be enzym...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5298413/ https://www.ncbi.nlm.nih.gov/pubmed/27208213 http://dx.doi.org/10.1042/BJ20151195 |
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author | Stanley, Mathew Virdee, Satpal |
author_facet | Stanley, Mathew Virdee, Satpal |
author_sort | Stanley, Mathew |
collection | PubMed |
description | The modification of proteins with ubiquitin (Ub) is an important regulator of eukaryotic biology and deleterious perturbation of this process is widely linked to the onset of various diseases. The regulatory capacity of the Ub signal is high and, in part, arises from the capability of Ub to be enzymatically polymerised to form polyubiquitin (polyUb) chains of eight different linkage types. These distinct polyUb topologies can then be site-specifically conjugated to substrate proteins to elicit a number of cellular outcomes. Therefore, to further elucidate the biological significance of substrate ubiquitination, methodologies that allow the production of defined polyUb species, and substrate proteins that are site-specifically modified with them, are essential to progress our understanding. Many chemically inspired methods have recently emerged which fulfil many of the criteria necessary for achieving deeper insight into Ub biology. With a view to providing immediate impact in traditional biology research labs, the aim of this review is to provide an overview of the techniques that are available for preparing Ub conjugates and polyUb chains with focus on approaches that use recombinant protein building blocks. These approaches either produce a native isopeptide, or analogue thereof, that can be hydrolysable or non-hydrolysable by deubiquitinases. The most significant biological insights that have already been garnered using such approaches will also be summarized. |
format | Online Article Text |
id | pubmed-5298413 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-52984132017-02-21 Chemical ubiquitination for decrypting a cellular code Stanley, Mathew Virdee, Satpal Biochem J Review Articles The modification of proteins with ubiquitin (Ub) is an important regulator of eukaryotic biology and deleterious perturbation of this process is widely linked to the onset of various diseases. The regulatory capacity of the Ub signal is high and, in part, arises from the capability of Ub to be enzymatically polymerised to form polyubiquitin (polyUb) chains of eight different linkage types. These distinct polyUb topologies can then be site-specifically conjugated to substrate proteins to elicit a number of cellular outcomes. Therefore, to further elucidate the biological significance of substrate ubiquitination, methodologies that allow the production of defined polyUb species, and substrate proteins that are site-specifically modified with them, are essential to progress our understanding. Many chemically inspired methods have recently emerged which fulfil many of the criteria necessary for achieving deeper insight into Ub biology. With a view to providing immediate impact in traditional biology research labs, the aim of this review is to provide an overview of the techniques that are available for preparing Ub conjugates and polyUb chains with focus on approaches that use recombinant protein building blocks. These approaches either produce a native isopeptide, or analogue thereof, that can be hydrolysable or non-hydrolysable by deubiquitinases. The most significant biological insights that have already been garnered using such approaches will also be summarized. Portland Press Ltd. 2016-05-11 2016-05-15 /pmc/articles/PMC5298413/ /pubmed/27208213 http://dx.doi.org/10.1042/BJ20151195 Text en © 2016 The Author(s) https://creativecommons.org/licenses/by/4.0/ This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0) . |
spellingShingle | Review Articles Stanley, Mathew Virdee, Satpal Chemical ubiquitination for decrypting a cellular code |
title | Chemical ubiquitination for decrypting a cellular
code |
title_full | Chemical ubiquitination for decrypting a cellular
code |
title_fullStr | Chemical ubiquitination for decrypting a cellular
code |
title_full_unstemmed | Chemical ubiquitination for decrypting a cellular
code |
title_short | Chemical ubiquitination for decrypting a cellular
code |
title_sort | chemical ubiquitination for decrypting a cellular
code |
topic | Review Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5298413/ https://www.ncbi.nlm.nih.gov/pubmed/27208213 http://dx.doi.org/10.1042/BJ20151195 |
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