ArticleThe Journal of biological chemistry2009
A non-canonical MEK/ERK signaling pathway regulates autophagy via regulating Beclin 1.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 198 papers.
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Who cites it
198 citing papers in PubMed, 318 citations in OpenAlex.
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- Muscle protein breakdown has a minor role in the protein anabolic response to essential amino acid and carbohydrate intake following resistance exercise.American journal of physiology. Regulatory, integrative and comparative physiology · 2010Trial
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- Regulation of autophagy by the p53 family and the implications for cancer therapies.Discover oncology · 2026Review
- Stanniocalcin 2-Induced Autophagy Confers Resistance of Lung Cancer Cells to EGFR Inhibition via the ERK/Beclin 1 Signaling.Cancer medicine · 2026Article
- The clinical implications of zinc and copper levels in COPD patients: a narrative review.Annals of medicine and surgery (2012) · 2025Review
- SCAMP3-Driven Regulation of ERK1/2 and Autophagy Phosphoproteomics Signatures in Triple-Negative Breast Cancer.International journal of molecular sciences · 2025Article
- Review
- Autophagy in brain tumors: molecular mechanisms, challenges, and therapeutic opportunities.Journal of translational medicine · 2025Review
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- Guts for Self-Eating: Role of Autophagy in Gastrointestinal Health and Disease.Gastro hep advances · 2025Review
- Controversial Roles of Autophagy in Adenomyosis and Its Implications for Fertility Outcomes-A Systematic Review.Journal of clinical medicine · 2024Review
- Mechanistic complement of autosomal dominant polycystic kidney disease: the role of aquaporins.Journal of molecular medicine (Berlin, Germany) · 2024Review
- Emerging Molecular and Synaptic Targets for the Management of Chronic Pain Caused by Systemic Lupus Erythematosus.International journal of molecular sciences · 2024Review
- Forchlorfenuron-Induced Mitochondrial Respiration Inhibition and Metabolic Shifts in Endometrial Cancer.Cancers · 2024Article
- Atg5 knockout induces alternative autophagy via the downregulation of Akt expression.Toxicological research · 2023Article
- Cadmium affects autophagy in the human intestinal cells Caco-2 through ROS-mediated ERK activation.Cell biology and toxicology · 2023Article
- Arginine deiminase produced by lactic acid bacteria as a potent anti-cancer drug.Medical oncology (Northwood, London, England) · 2023Review
- Review
138 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autophagy-essential proteins are the molecular basis of protective or destructive autophagy machinery. However, little is known about the signaling mechanisms governing these proteins and the opposing consequences of autophagy in mammals. Here we report that a non-canonical MEK/ERK module, which is positioned downstream of AMP-activated protein kinase (AMPK) and upstream of tuberous sclerosis complex (TSC), regulates autophagy by regulating Beclin 1. Depletion of ERK partially inhibited autophagy, whereas specific inhibition on MEK completely inhibited autophagy. MEK could bypass ERK to promote autophagy. Basal MEK/ERK activity conferred basal Beclin 1 by preventing disassembly of mammalian target of rapamycin complex 1 (mTORC1) and mTORC2. Activation of MEK/ERK by AMPK upon autophagy stimuli disassembled mTORC1 via binding to and activating TSC but disassembled mTORC2 independently of TSC. Inhibition of mTORC1 or mTORC2 by transiently or moderately activated MEK/ERK caused moderately enhanced Beclin 1 resulting in cytoprotective autophagy, whereas inhibition of both mTORC1 and mTORC2 by sustained MEK/ERK activation caused strongly pronounced Beclin 1 leading to cytodestructive autophagy. Our findings thus propose that the AMPK-MEK/ERK-TSC-mTOR pathway regulation of Beclin 1 represents different thresholds responsible for a protective or destructive autophagy.
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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.