ArticleProceedings of the National Academy of Sciences of the United States of America2015
mTOR inhibition activates overall protein degradation by the ubiquitin proteasome system as well as by autophagy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 295 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
295 citing papers in PubMed, 2 syntheses or guidelines pooled it, 477 citations in OpenAlex.
- Metabolic transitions define spermatogonial stem cell maturation.Human reproduction (Oxford, England) · 2022Pooled it
- The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.Pharmacology & therapeutics · 2020Pooled it
- Ceritinib overcomes proteasome inhibitor resistance in multiple myeloma by suppressing the protein folding response.Haematologica · 2026Article
- Ubiquitin receptor-mediated, ubiquitin-independent targeted protein degradation via 26Science advances · 2026Article
- Maternal redd1 mRNA decline triggers mTORC1 activation during the blastula-gastrula transition in zebrafish embryos.The FEBS journal · 2026Article
- Stimulating proteasomal degradation in human proteinopathies.The FEBS journal · 2026Review
- Autophagy Modulation in Cancer Therapy: Navigating the Dual Roles to Overcome Chemoresistance.Health science reports · 2026Article
- Glucosamine Promotes Autophagy and Attenuates Hepatic Steatosis Via O-GlcNAcylation-Mediated Mechanisms.Journal of biochemical and molecular toxicology · 2026Article
- Cholesterol at the Center of Alzheimer's Disease: A Unifying Hypothesis on the Pathogenic Mechanism.Molecules (Basel, Switzerland) · 2026Review
- mTOR inhibition augments antitumor immune effector response by reprogramming thebioRxiv : the preprint server for biology · 2026Article
- Mechanical Loading Induces the Radial Growth of Myofibrils and Myofibrillogenesis via an mTORC1-Dependent Mechanism.bioRxiv : the preprint server for biology · 2026Article
- Regulation of gene expression by alternative polyadenylation in health and disease.Nature reviews. Genetics · 2026Review
- USP10 deubiquitinase: Physiological function, diseases and therapeutic target (Review).International journal of molecular medicine · 2026Review
- Mitochondrial iron overload is associated with lysosomal dysfunction-mediated mitophagy impairment in the heart of Friedreich's ataxia.Mitochondrion · 2026Article
- Autophagy in cancer nanomedicine: an implication of nanomaterials' impact on the evolutionarily conservative catabolic processes in human tumors.Archives of toxicology · 2026Review
- Phosphatidylinositol transfer protein-1 integrates insulin/IGF-1 and TOR signaling to negatively regulate lifespan and healthspan in Caenorhabditis elegans.Journal of biomedical science · 2026Article
- An Updated Narrative Review on the Therapeutic Potential of Resveratrol in the Treatment of Cancer.Health science reports · 2026Article
- HIV-1 Vpr is targeted for degradation by autophagy.PLoS pathogens · 2026Article
- Sotatercept for the treatment of portopulmonary hypertension: a case report.Communications medicine · 2026Article
- Virus-mediated changes in insect vector tolerance to a neonicotinoid insecticide.Scientific reports · 2026Article
235 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Growth factors and nutrients enhance protein synthesis and suppress overall protein degradation by activating the protein kinase mammalian target of rapamycin (mTOR). Conversely, nutrient or serum deprivation inhibits mTOR and stimulates protein breakdown by inducing autophagy, which provides the starved cells with amino acids for protein synthesis and energy production. However, it is unclear whether proteolysis by the ubiquitin proteasome system (UPS), which catalyzes most protein degradation in mammalian cells, also increases when mTOR activity decreases. Here we show that inhibiting mTOR with rapamycin or Torin1 rapidly increases the degradation of long-lived cell proteins, but not short-lived ones, by stimulating proteolysis by proteasomes, in addition to autophagy. This enhanced proteasomal degradation required protein ubiquitination, and within 30 min after mTOR inhibition, the cellular content of K48-linked ubiquitinated proteins increased without any change in proteasome content or activity. This rapid increase in UPS-mediated proteolysis continued for many hours and resulted primarily from inhibition of mTORC1 (not mTORC2), but did not require new protein synthesis or key mTOR targets: S6Ks, 4E-BPs, or Ulks. These findings do not support the recent report that mTORC1 inhibition reduces proteolysis by suppressing proteasome expression [Zhang Y, et al. (2014) Nature 513(7518):440-443]. Several growth-related proteins were identified that were ubiquitinated and degraded more rapidly after mTOR inhibition, including HMG-CoA synthase, whose enhanced degradation probably limits cholesterol biosynthesis upon insulin deficiency. Thus, mTOR inhibition coordinately activates the UPS and autophagy, which provide essential amino acids and, together with the enhanced ubiquitination of anabolic proteins, help slow growth.
Indexed as
Identifiers
What OpenQuestion holds
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.