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Site-Specific Proteasome Inhibitors

Proteasome is a multi-subunit protein degradation machine, which plays a key role in the maintenance of protein homeostasis and, through degradation of regulatory proteins, in the regulation of numerous cell functions. Proteasome inhibitors are essential tools for biomedical research. Three proteaso...

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Detalles Bibliográficos
Autor principal: Kisselev, Alexei F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8773591/
https://www.ncbi.nlm.nih.gov/pubmed/35053202
http://dx.doi.org/10.3390/biom12010054
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author Kisselev, Alexei F.
author_facet Kisselev, Alexei F.
author_sort Kisselev, Alexei F.
collection PubMed
description Proteasome is a multi-subunit protein degradation machine, which plays a key role in the maintenance of protein homeostasis and, through degradation of regulatory proteins, in the regulation of numerous cell functions. Proteasome inhibitors are essential tools for biomedical research. Three proteasome inhibitors, bortezomib, carfilzomib, and ixazomib are approved by the FDA for the treatment of multiple myeloma; another inhibitor, marizomib, is undergoing clinical trials. The proteolytic core of the proteasome has three pairs of active sites, β5, β2, and β1. All clinical inhibitors and inhibitors that are widely used as research tools (e.g., epoxomicin, MG-132) inhibit multiple active sites and have been extensively reviewed in the past. In the past decade, highly specific inhibitors of individual active sites and the distinct active sites of the lymphoid tissue-specific immunoproteasome have been developed. Here, we provide a comprehensive review of these site-specific inhibitors of mammalian proteasomes and describe their utilization in the studies of the biology of the active sites and their roles as drug targets for the treatment of different diseases.
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spelling pubmed-87735912022-01-21 Site-Specific Proteasome Inhibitors Kisselev, Alexei F. Biomolecules Review Proteasome is a multi-subunit protein degradation machine, which plays a key role in the maintenance of protein homeostasis and, through degradation of regulatory proteins, in the regulation of numerous cell functions. Proteasome inhibitors are essential tools for biomedical research. Three proteasome inhibitors, bortezomib, carfilzomib, and ixazomib are approved by the FDA for the treatment of multiple myeloma; another inhibitor, marizomib, is undergoing clinical trials. The proteolytic core of the proteasome has three pairs of active sites, β5, β2, and β1. All clinical inhibitors and inhibitors that are widely used as research tools (e.g., epoxomicin, MG-132) inhibit multiple active sites and have been extensively reviewed in the past. In the past decade, highly specific inhibitors of individual active sites and the distinct active sites of the lymphoid tissue-specific immunoproteasome have been developed. Here, we provide a comprehensive review of these site-specific inhibitors of mammalian proteasomes and describe their utilization in the studies of the biology of the active sites and their roles as drug targets for the treatment of different diseases. MDPI 2021-12-31 /pmc/articles/PMC8773591/ /pubmed/35053202 http://dx.doi.org/10.3390/biom12010054 Text en © 2021 by the author. 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
Kisselev, Alexei F.
Site-Specific Proteasome Inhibitors
title Site-Specific Proteasome Inhibitors
title_full Site-Specific Proteasome Inhibitors
title_fullStr Site-Specific Proteasome Inhibitors
title_full_unstemmed Site-Specific Proteasome Inhibitors
title_short Site-Specific Proteasome Inhibitors
title_sort site-specific proteasome inhibitors
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8773591/
https://www.ncbi.nlm.nih.gov/pubmed/35053202
http://dx.doi.org/10.3390/biom12010054
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