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Ubiquitin Ligases at the Heart of Skeletal Muscle Atrophy Control

Skeletal muscle loss is a detrimental side-effect of numerous chronic diseases that dramatically increases mortality and morbidity. The alteration of protein homeostasis is generally due to increased protein breakdown while, protein synthesis may also be down-regulated. The ubiquitin proteasome syst...

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Autores principales: Peris-Moreno, Dulce, Cussonneau, Laura, Combaret, Lydie, Polge, Cécile, Taillandier, Daniel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829870/
https://www.ncbi.nlm.nih.gov/pubmed/33466753
http://dx.doi.org/10.3390/molecules26020407
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author Peris-Moreno, Dulce
Cussonneau, Laura
Combaret, Lydie
Polge, Cécile
Taillandier, Daniel
author_facet Peris-Moreno, Dulce
Cussonneau, Laura
Combaret, Lydie
Polge, Cécile
Taillandier, Daniel
author_sort Peris-Moreno, Dulce
collection PubMed
description Skeletal muscle loss is a detrimental side-effect of numerous chronic diseases that dramatically increases mortality and morbidity. The alteration of protein homeostasis is generally due to increased protein breakdown while, protein synthesis may also be down-regulated. The ubiquitin proteasome system (UPS) is a master regulator of skeletal muscle that impacts muscle contractile properties and metabolism through multiple levers like signaling pathways, contractile apparatus degradation, etc. Among the different actors of the UPS, the E3 ubiquitin ligases specifically target key proteins for either degradation or activity modulation, thus controlling both pro-anabolic or pro-catabolic factors. The atrogenes MuRF1/TRIM63 and MAFbx/Atrogin-1 encode for key E3 ligases that target contractile proteins and key actors of protein synthesis respectively. However, several other E3 ligases are involved upstream in the atrophy program, from signal transduction control to modulation of energy balance. Controlling E3 ligases activity is thus a tempting approach for preserving muscle mass. While indirect modulation of E3 ligases may prove beneficial in some situations of muscle atrophy, some drugs directly inhibiting their activity have started to appear. This review summarizes the main signaling pathways involved in muscle atrophy and the E3 ligases implicated, but also the molecules potentially usable for future therapies.
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spelling pubmed-78298702021-01-26 Ubiquitin Ligases at the Heart of Skeletal Muscle Atrophy Control Peris-Moreno, Dulce Cussonneau, Laura Combaret, Lydie Polge, Cécile Taillandier, Daniel Molecules Review Skeletal muscle loss is a detrimental side-effect of numerous chronic diseases that dramatically increases mortality and morbidity. The alteration of protein homeostasis is generally due to increased protein breakdown while, protein synthesis may also be down-regulated. The ubiquitin proteasome system (UPS) is a master regulator of skeletal muscle that impacts muscle contractile properties and metabolism through multiple levers like signaling pathways, contractile apparatus degradation, etc. Among the different actors of the UPS, the E3 ubiquitin ligases specifically target key proteins for either degradation or activity modulation, thus controlling both pro-anabolic or pro-catabolic factors. The atrogenes MuRF1/TRIM63 and MAFbx/Atrogin-1 encode for key E3 ligases that target contractile proteins and key actors of protein synthesis respectively. However, several other E3 ligases are involved upstream in the atrophy program, from signal transduction control to modulation of energy balance. Controlling E3 ligases activity is thus a tempting approach for preserving muscle mass. While indirect modulation of E3 ligases may prove beneficial in some situations of muscle atrophy, some drugs directly inhibiting their activity have started to appear. This review summarizes the main signaling pathways involved in muscle atrophy and the E3 ligases implicated, but also the molecules potentially usable for future therapies. MDPI 2021-01-14 /pmc/articles/PMC7829870/ /pubmed/33466753 http://dx.doi.org/10.3390/molecules26020407 Text en © 2021 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Peris-Moreno, Dulce
Cussonneau, Laura
Combaret, Lydie
Polge, Cécile
Taillandier, Daniel
Ubiquitin Ligases at the Heart of Skeletal Muscle Atrophy Control
title Ubiquitin Ligases at the Heart of Skeletal Muscle Atrophy Control
title_full Ubiquitin Ligases at the Heart of Skeletal Muscle Atrophy Control
title_fullStr Ubiquitin Ligases at the Heart of Skeletal Muscle Atrophy Control
title_full_unstemmed Ubiquitin Ligases at the Heart of Skeletal Muscle Atrophy Control
title_short Ubiquitin Ligases at the Heart of Skeletal Muscle Atrophy Control
title_sort ubiquitin ligases at the heart of skeletal muscle atrophy control
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829870/
https://www.ncbi.nlm.nih.gov/pubmed/33466753
http://dx.doi.org/10.3390/molecules26020407
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