Identification of the MuRF1 Skeletal Muscle Ubiquitylome Through Quantitative Proteomics.
MuRF1
electroporation
muscle atrophy
protein degradation
ubiquitin proteomics
Journal
Function (Oxford, England)
ISSN: 2633-8823
Titre abrégé: Function (Oxf)
Pays: England
ID NLM: 101770668
Informations de publication
Date de publication:
2021
2021
Historique:
received:
23
02
2021
revised:
12
05
2021
accepted:
17
05
2021
entrez:
28
6
2021
pubmed:
29
6
2021
medline:
29
6
2021
Statut:
epublish
Résumé
MuRF1 (TRIM63) is a muscle-specific E3 ubiquitin ligase and component of the ubiquitin proteasome system. MuRF1 is transcriptionally upregulated under conditions that cause muscle loss, in both rodents and humans, and is a recognized marker of muscle atrophy. In this study, we used in vivo electroporation to determine whether MuRF1 overexpression alone can cause muscle atrophy and, in combination with ubiquitin proteomics, identify the endogenous MuRF1 substrates in skeletal muscle. Overexpression of MuRF1 in adult mice increases ubiquitination of myofibrillar and sarcoplasmic proteins, increases expression of genes associated with neuromuscular junction instability, and causes muscle atrophy. A total of 169 ubiquitination sites on 56 proteins were found to be regulated by MuRF1. MuRF1-mediated ubiquitination targeted both thick and thin filament contractile proteins, as well as, glycolytic enzymes, deubiquitinases, p62, and VCP. These data reveal a potential role for MuRF1 in not only the breakdown of the sarcomere but also the regulation of metabolism and other proteolytic pathways in skeletal muscle.
Identifiants
pubmed: 34179788
doi: 10.1093/function/zqab029
pii: zqab029
pmc: PMC8218097
doi:
Substances chimiques
Ubiquitin
0
Ubiquitin-Protein Ligases
EC 2.3.2.27
Trim63 protein, mouse
EC 2.3.2.27
Muscle Proteins
0
Tripartite Motif Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Pagination
zqab029Subventions
Organisme : NIAMS NIH HHS
ID : R01 AR070031
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM137961
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of American Physiological Society.
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