ArticleAutophagy2021
AMPK-dependent phosphorylation is required for transcriptional activation of TFEB and TFE3.
Article in Autophagy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers.
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Who cites it
140 citing papers in PubMed, 214 citations in OpenAlex.
- Exercise-induced lysosomal adaptations in skeletal muscle.Sports medicine and health science · 2026Review
- A role for CASM in the repair of damaged Golgi architecture.Autophagy · 2026Article
- AMPK as a central regulator of necroptosis: mechanistic insights and therapeutic implications.Journal of physiology and biochemistry · 2026Review
- Dilating the aging clock with light.Innovation (Cambridge (Mass.)) · 2026Review
- Wogonin, a bioactive flavonoid from Scutellaria baicalensis, alleviates alcoholic pancreatitis via AMPK-mediated TFEB activation.Journal of advanced research · 2026Article
- TFEB Antagonizes Cardiac Hypertrophy and Failure by Enhancing Lysosomal Capacity and Mitochondrial Function.Circulation research · 2026Article
- Microglial mitophagy as an immunometabolic checkpoint in alzheimer's disease: linking mitochondrial quality control to neuroinflammation.Journal of neuroinflammation · 2026Review
- Crosstalk collapse: mitochondria-centric organelle network disruption in ovarian aging.Cell communication and signaling : CCS · 2026Review
- Tumor growth suppression of ivermectin in gastric cancer cell lines and primary gastric cancer organoids.Journal of gastrointestinal oncology · 2026Article
- Transcriptional and epigenetic regulation of autophagy: mechanisms, disease relevance and therapeutic opportunities.Signal transduction and targeted therapy · 2026Review
- AMPK promotes TFEB transcriptional activity through dephosphorylation at both MTORC1-dependent and -independent sites.Autophagy · 2026Article
- NIBV Induces Incomplete Autophagy via AMPK-TFEB, Causing Kidney Injury in Chicks.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- How Polyphenol Metabolites Spatiotemporally Reprogram Transcription Factors and Human Proteostasis: A Metabolite-Centric Framework.Current issues in molecular biology · 2026Review
- Modulation of the AMPK/TFEB Axis by Ezetimibe Attenuates Neuroinflammatory, Oxidative Stress, and Neurotransmitter Dysregulation in Naloxone-precipitated Tramadol Withdrawal in Mice.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026Article
- TFEB degradation is regulated by an IKK/β-TrCP2 phosphorylation-ubiquitination cascade.Nature communications · 2026Article
- Deciphering the role of SIRT6 in suppressing the AMPK-mTOR-TFEB axis: regulation of autophagy activation in HCC.Cancer gene therapy · 2026Article
- Apoptotic bodies derived from human umbilical cord mesenchymal stem cells improve recovery from myocardial infarction in swine.Autophagy · 2026Article
- Impaired Autophagic Flux in Adipose Tissue Aggravates Pancreatic Injury in Obesity-Related Severe Acute Pancreatitis.Immunity, inflammation and disease · 2026Article
- [Poricoic acid A alleviates dextran sulfate sodium-induced colitis in mice by regulating AMPK/mTOR-mediated autophagy and inhibiting intestinal epithelial cell apoptosis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- Endoplasmic reticulum stress-mediated cell death in spinal cord injury: from molecular mechanisms to therapeutic applications.Frontiers in cell and developmental biology · 2026Review
80 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Increased macroautophagy/autophagy and lysosomal activity promote tumor growth, survival and chemo-resistance. During acute starvation, autophagy is rapidly engaged by AMPK (AMP-activated protein kinase) activation and MTOR (mechanistic target of rapamycin kinase) complex 1 (MTORC1) inhibition to maintain energy homeostasis and cell survival. TFEB (transcription factor E3) and TFE3 (transcription factor binding to IGHM enhancer 3) are master transcriptional regulators of autophagy and lysosomal activity and their cytoplasm/nuclear shuttling is controlled by MTORC1-dependent multisite phosphorylation. However, it is not known whether and how the transcriptional activity of TFEB or TFE3 is regulated. We show that AMPK mediates phosphorylation of TFEB and TFE3 on three serine residues, leading to TFEB and TFE3 transcriptional activity upon nutrient starvation, FLCN (folliculin) depletion and pharmacological manipulation of MTORC1 or AMPK. Collectively, we show that MTORC1 specifically controls TFEB and TFE3 cytosolic retention, whereas AMPK is essential for TFEB and TFE3 transcriptional activity. This dual and opposing regulation of TFEB and TFE3 by MTORC1 and AMPK is reminiscent of the regulation of another critical regulator of autophagy, ULK1 (unc-51 like autophagy activating kinase 1). Surprisingly, we show that chemoresistance is mediated by AMPK-dependent activation of TFEB, which is abolished by pharmacological inhibition of AMPK or mutation of serine 466, 467 and 469 to alanine residues within TFEB. Altogether, we show that AMPK is a key regulator of TFEB and TFE3 transcriptional activity, and we validate AMPK as a promising target in cancer therapy to evade chemotherapeutic resistance.
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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.