ArticleNature cell biology2013
mTOR inhibits autophagy by controlling ULK1 ubiquitylation, self-association and function through AMBRA1 and TRAF6.
Article in Nature cell biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 487 papers, 1 of them a synthesis that pooled it.
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Who cites it
487 citing papers in PubMed, 1 synthesis or guideline pooled it, 763 citations in OpenAlex.
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- The role of autophagy in spinal cord injury: Mechanisms, crosstalk, and therapeutic strategies.Neural regeneration research · 2026Article
- Multiplexed perturbation enables scalable pooled screens.Nature methods · 2026Article
- The Effect of Resistance Training and Ursolic Acid on the PI3K-AKT-mTOR Pathway in Aged Diabetic Rats: A Comparative Study.Aging medicine (Milton (N.S.W)) · 2026Article
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- Ubiquitin ligase RCHY1 regulates autophagosome-lysosome fusion.Cell death discovery · 2026Article
- Targeting macropinocytosis for cancer therapy.Nature reviews. Cancer · 2026Review
- MicroRNA-451 Modulates Autophagy-Related Signaling with Relevance to Renal Fibrosis in an Accelerated Mouse Model of Diabetic Kidney Disease.Current issues in molecular biology · 2026Article
- Positive Feedback Loop of Histone Lactylation-Driven HNRNPC Promotes Autophagy to Confer Pancreatic Ductal Adenocarcinoma Gemcitabine Resistance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- LncRNA P4HA2-AS1 drives renal interstitial fibrosis via trim32-mediated k63 ubiquitination of ULK1 and autophagic dysregulation.Communications biology · 2026Article
- CRL4International journal of biological sciences · 2026Article
- The role of autophagy in protozoan infections.Frontiers in cellular and infection microbiology · 2026Review
- Dual targeting of the UPS and autophagy as a novel therapy for neurodegenerative proteinopathies.Frontiers in cellular neuroscience · 2026Review
427 more citing papers are in PubMed but not listed here.
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11 authors at 5 institutions in 2 countries.
Funding
Abstract
Autophagy is important in the basal or stress-induced clearance of bulk cytosol, damaged organelles, pathogens and selected proteins by specific vesicles, the autophagosomes. Following mTOR (mammalian target of rapamycin) inhibition, autophagosome formation is primed by the ULK1 and the beclin-1-Vps34-AMBRA1 complexes, which are linked together by a scaffold platform, the exocyst. Although several regulative steps have been described along this pathway, few targets of mTOR are known, and the cross-talk between ULK1 and beclin 1 complexes is still not fully understood. We show that under non-autophagic conditions, mTOR inhibits AMBRA1 by phosphorylation, whereas on autophagy induction, AMBRA1 is dephosphorylated. In this condition, AMBRA1, interacting with the E3-ligase TRAF6, supports ULK1 ubiquitylation by LYS-63-linked chains, and its subsequent stabilization, self-association and function. As ULK1 has been shown to activate AMBRA1 by phosphorylation, the proposed pathway may act as a positive regulation loop, which may be targeted in human disorders linked to impaired autophagy.
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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.