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On the Study of Deubiquitinases: Using the Right Tools for the Job
Deubiquitinases (DUBs) have been the subject of intense scrutiny in recent years. Many of their diverse enzymatic mechanisms are well characterized in vitro; however, our understanding of these enzymes at the cellular level lags due to the lack of quality tool reagents. DUBs play a role in seemingly...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9139131/ https://www.ncbi.nlm.nih.gov/pubmed/35625630 http://dx.doi.org/10.3390/biom12050703 |
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author | Caba, Cody Mohammadzadeh, Azam Tong, Yufeng |
author_facet | Caba, Cody Mohammadzadeh, Azam Tong, Yufeng |
author_sort | Caba, Cody |
collection | PubMed |
description | Deubiquitinases (DUBs) have been the subject of intense scrutiny in recent years. Many of their diverse enzymatic mechanisms are well characterized in vitro; however, our understanding of these enzymes at the cellular level lags due to the lack of quality tool reagents. DUBs play a role in seemingly every biological process and are central to many human pathologies, thus rendering them very desirable and challenging therapeutic targets. This review aims to provide researchers entering the field of ubiquitination with knowledge of the pharmacological modulators and tool molecules available to study DUBs. A focus is placed on small molecule inhibitors, ubiquitin variants (UbVs), and activity-based probes (ABPs). Leveraging these tools to uncover DUB biology at the cellular level is of particular importance and may lead to significant breakthroughs. Despite significant drug discovery efforts, only approximately 15 chemical probe-quality small molecule inhibitors have been reported, hitting just 6 of about 100 DUB targets. UbV technology is a promising approach to rapidly expand the library of known DUB inhibitors and may be used as a combinatorial platform for structure-guided drug design. |
format | Online Article Text |
id | pubmed-9139131 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91391312022-05-28 On the Study of Deubiquitinases: Using the Right Tools for the Job Caba, Cody Mohammadzadeh, Azam Tong, Yufeng Biomolecules Review Deubiquitinases (DUBs) have been the subject of intense scrutiny in recent years. Many of their diverse enzymatic mechanisms are well characterized in vitro; however, our understanding of these enzymes at the cellular level lags due to the lack of quality tool reagents. DUBs play a role in seemingly every biological process and are central to many human pathologies, thus rendering them very desirable and challenging therapeutic targets. This review aims to provide researchers entering the field of ubiquitination with knowledge of the pharmacological modulators and tool molecules available to study DUBs. A focus is placed on small molecule inhibitors, ubiquitin variants (UbVs), and activity-based probes (ABPs). Leveraging these tools to uncover DUB biology at the cellular level is of particular importance and may lead to significant breakthroughs. Despite significant drug discovery efforts, only approximately 15 chemical probe-quality small molecule inhibitors have been reported, hitting just 6 of about 100 DUB targets. UbV technology is a promising approach to rapidly expand the library of known DUB inhibitors and may be used as a combinatorial platform for structure-guided drug design. MDPI 2022-05-14 /pmc/articles/PMC9139131/ /pubmed/35625630 http://dx.doi.org/10.3390/biom12050703 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Caba, Cody Mohammadzadeh, Azam Tong, Yufeng On the Study of Deubiquitinases: Using the Right Tools for the Job |
title | On the Study of Deubiquitinases: Using the Right Tools for the Job |
title_full | On the Study of Deubiquitinases: Using the Right Tools for the Job |
title_fullStr | On the Study of Deubiquitinases: Using the Right Tools for the Job |
title_full_unstemmed | On the Study of Deubiquitinases: Using the Right Tools for the Job |
title_short | On the Study of Deubiquitinases: Using the Right Tools for the Job |
title_sort | on the study of deubiquitinases: using the right tools for the job |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9139131/ https://www.ncbi.nlm.nih.gov/pubmed/35625630 http://dx.doi.org/10.3390/biom12050703 |
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