ArticleNature communications2021
Antagonistic control of myofiber size and muscle protein quality control by the ubiquitin ligase UBR4 during aging.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
What it found
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Who cites it
51 citing papers in PubMed, 70 citations in OpenAlex.
- UBA1 knockdown dysregulates UBA1-sensitive proteins and impairs muscle function in models of spinal muscular atrophy X-linked 2.Disease models & mechanisms · 2026Article
- Systemic and cardiac pathology induced by a clinically relevant USP8 activating mutation.Disease models & mechanisms · 2026Article
- Structure-function relationship of alpha-synuclein fibrillar polymorphs derived from distinct synucleinopathies.Molecular systems biology · 2026Article
- Review
- Largely Distinct Post-Translational Modifications Differentiate Skeletal Muscle Wasting Caused by Cancer, Dexamethasone and Aging.Journal of cachexia, sarcopenia and muscle · 2026Article
- Organ-Specific Regulation of Systemic Aging: Focus on the Brain, Skeletal Muscle, and Gut.Cells · 2026Review
- Position effect variegation (PEV) as an aging clock: visualization of age-dependent loss of heterochromatin and longevity associated with enhanced heterochromatin.Scientific reports · 2026Article
- Response of UBR-box E3 ubiquitin ligases and protein quality control pathways to perturbations in protein synthesis and skeletal muscle size.American journal of physiology. Cell physiology · 2025Article
- Muscle Cathepsin B Treatment Improves Behavioral and Neurogenic Deficits in a Mouse Model of Alzheimer's Disease.Aging cell · 2025Article
- Response of UBR-box E3 ubiquitin ligases and protein quality control pathways to perturbations in protein synthesis and skeletal muscle size.bioRxiv : the preprint server for biology · 2025Article
- UBR5: A New Player in Protein Quality Control for Skeletal Muscle Growth and Remodeling.Exercise and sport sciences reviews · 2025Review
- Architecture of the UBR4 complex, a giant E4 ligase central to eukaryotic protein quality control.Science (New York, N.Y.) · 2025Article
- Article
- Tumor-promoting UBR4 coordinates impaired mitophagy-associated senescence and lung adenocarcinoma pathogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Androgens as the "old age stick" in skeletal muscle.Cell communication and signaling : CCS · 2025Review
- Article
- Chaperone Proteins: The Rising Players in Muscle Atrophy.Journal of cachexia, sarcopenia and muscle · 2025Review
- Methylome-proteome integration after late-life voluntary exercise training reveals regulation and target information for improved skeletal muscle health.The Journal of physiology · 2025Article
- The ubiquitin-conjugating enzyme UBE2D maintains a youthful proteome and ensures protein quality control during aging by sustaining proteasome activity.PLoS biology · 2025Article
- Ubiquitin E3 ligases in the plant Arg/N-degron pathway.The Biochemical journal · 2024Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Sarcopenia is a degenerative condition that consists in age-induced atrophy and functional decline of skeletal muscle cells (myofibers). A common hypothesis is that inducing myofiber hypertrophy should also reinstate myofiber contractile function but such model has not been extensively tested. Here, we find that the levels of the ubiquitin ligase UBR4 increase in skeletal muscle with aging, and that UBR4 increases the proteolytic activity of the proteasome. Importantly, muscle-specific UBR4 loss rescues age-associated myofiber atrophy in mice. However, UBR4 loss reduces the muscle specific force and accelerates the decline in muscle protein quality that occurs with aging in mice. Similarly, hypertrophic signaling induced via muscle-specific loss of UBR4/poe and of ESCRT members (HGS/Hrs, STAM, USP8) that degrade ubiquitinated membrane proteins compromises muscle function and shortens lifespan in Drosophila by reducing protein quality control. Altogether, these findings indicate that these ubiquitin ligases antithetically regulate myofiber size and muscle protein quality control.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.