Journal article
Identification of the MuRF1 Skeletal Muscle Ubiquitylome Through Quantitative Proteomics
Function (Oxford, England), Vol.2(4), pp.zqab029-zqab029
01/01/2021
DOI: 10.1093/function/zqab029
PMCID: PMC8218097
PMID: 34179788
Abstract
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.
Details
- Title: Subtitle
- Identification of the MuRF1 Skeletal Muscle Ubiquitylome Through Quantitative Proteomics
- Creators
- Leslie M. Baehr - Roy J. and Lucille A. Carver College of MedicineDavid C. Hughes - Roy J. and Lucille A. Carver College of MedicineSarah A. Lynch - University of North FloridaDelphi Van Haver - Ghent University HospitalTeresa Mendes Maia - Ghent University HospitalAndrea G. Marshall - Roy J. and Lucille A. Carver College of MedicineLilliana Radoshevich - Roy J. and Lucille A. Carver College of MedicineFrancis Impens - Ghent University HospitalDavid S. Waddell - University of North FloridaSue C Bodine - Roy J. and Lucille A. Carver College of Medicine
- Resource Type
- Journal article
- Publication Details
- Function (Oxford, England), Vol.2(4), pp.zqab029-zqab029
- Publisher
- Oxford Univ Press
- DOI
- 10.1093/function/zqab029
- PMID
- 34179788
- PMCID
- PMC8218097
- ISSN
- 2633-8823
- eISSN
- 2633-8823
- Number of pages
- 18
- Grant note
- G0F8616N / Research Foundation Flanders (FWO); FWO R01 AR070031 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 01/01/2021
- Academic Unit
- Molecular Physiology and Biophysics; Microbiology and Immunology; Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984297541002771
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