ArticleCommunications biology2022
Dual roles of mTORC1-dependent activation of the ubiquitin-proteasome system in muscle proteostasis.
Article in Communications biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 43 citations in OpenAlex.
- Quantitative interactome mapping of skeletal muscle insulin resistance.Molecular systems biology · 2026Article
- Treating age-related loss of muscle mass and function: Where should we be focusing?The Journal of physiology · 2026Review
- Site-specific myopathy differences between spine and limb muscles: a kyphotic TSC1mKO mice model study.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2026Article
- The Age-Dependent Resident Myonuclear Multi-Omic Response to an Acute Skeletal Muscle Hypertrophic Stimulus in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mechanisms of protein degradation in atrophying muscles: What have we learned during the past decade?The Journal of biological chemistry · 2026Review
- Niclosamide extends health span and reduces frailty by ameliorating mTORC1 hyperactivation in aging models.Journal of advanced research · 2026Article
- Cell biomechanics on muscle atrophy: from intricate mechanisms to therapeutic frontiers.Annals of medicine · 2025Review
- 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
- Stigmasterol Protects Against Dexamethasone-Induced Muscle Atrophy by Modulating the FoxO3-MuRF1/MAFbx Signaling Pathway in C2C12 Myotubes and Mouse Skeletal Muscle.Biomolecules · 2025Article
- The Age-Dependent Resident Myonuclear Multi-Omic Response to a Skeletal Muscle Hypertrophic Stimulus.bioRxiv : the preprint server for biology · 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
- Effect of sarcopenia combined with Metabolic Syndrome (MS) on the prognosis of intertrochanteric fractures: a retrospective clinical study.BMC musculoskeletal disorders · 2025Article
- Article
- Suppressing proteasome activity enhances sensitivity to actinomycin D in diffuse anaplastic Wilms tumor.Cell reports. Medicine · 2025Article
- Muscle fiber Myc is dispensable for muscle growth and its forced expression severely perturbs homeostasis.Nature communications · 2025Article
- Actinomycin D and bortezomib disrupt protein homeostasis in Wilms tumor.bioRxiv : the preprint server for biology · 2024Article
- Deubiquitinases in muscle physiology and disorders.Biochemical Society transactions · 2024Review
- Advances in sarcopenia: mechanisms, therapeutic targets, and intervention strategies.Archives of pharmacal research · 2024Review
- Effects of hindlimb unloading on the mevalonate and mechanistic target of rapamycin complex 1 signaling pathways in a fast-twitch muscle in rats.Physiological reports · 2024Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Muscle size is controlled by the PI3K-PKB/Akt-mTORC1-FoxO pathway, which integrates signals from growth factors, energy and amino acids to activate protein synthesis and inhibit protein breakdown. While mTORC1 activity is necessary for PKB/Akt-induced muscle hypertrophy, its constant activation alone induces muscle atrophy. Here we show that this paradox is based on mTORC1 activity promoting protein breakdown through the ubiquitin-proteasome system (UPS) by simultaneously inducing ubiquitin E3 ligase expression via feedback inhibition of PKB/Akt and proteasome biogenesis via Nuclear Factor Erythroid 2-Like 1 (Nrf1). Muscle growth was restored by reactivation of PKB/Akt, but not by Nrf1 knockdown, implicating ubiquitination as the limiting step. However, both PKB/Akt activation and proteasome depletion by Nrf1 knockdown led to an immediate disruption of proteome integrity with rapid accumulation of damaged material. These data highlight the physiological importance of mTORC1-mediated PKB/Akt inhibition and point to juxtaposed roles of the UPS in atrophy and proteome integrity.
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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.