ArticleCell death and differentiation2021
eIF4A3 regulates the TFEB-mediated transcriptional response via GSK3B to control autophagy.
Article in Cell death and differentiation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
- Post-transcriptional activation of TGF-β signaling via SMAD mRNA stabilization by EIF4A3 promotes EMT and metastasis in gastric cancer.Cell biology and toxicology · 2026Article
- Mechanistic Elucidation of Yiqi Yangyin Qingre Decoction in Diabetic Nephropathy Therapy via Network Pharmacology and In Vivo Validation.Journal of diabetes research · 2026Article
- Triple-Target Inhibition of Cholinesterase, Amyloid Aggregation, and GSK3β to Ameliorate Cognitive Deficits and Neuropathology in the Triple-Transgenic Mouse Model of Alzheimer's Disease.Neuroscience bulletin · 2025Article
- D-mannose suppresses the angiogenesis and progression of colorectal cancer.Acta biochimica et biophysica Sinica · 2025Article
- Urolithin A inhibits breast cancer progression via activating TFEB-mediated mitophagy in tumor macrophages.Journal of advanced research · 2025Article
- MLKL-USP7-UBA52 signaling is indispensable for autophagy in brain through maintaining ubiquitin homeostasis.Autophagy · 2025Article
- Pellino 3 E3 ligase promotes starvation-induced autophagy to prevent hepatic steatosis.Science advances · 2025Article
- Post-transcriptional dynamics and RNA homeostasis in autophagy and cancer.Cell death and differentiation · 2025Review
- Signature and function of plasma exosome-derived circular RNAs in patients with hypertensive intracerebral hemorrhage.Molecular genetics and genomics : MGG · 2024Article
- PRKAA2, MTOR, and TFEB in the regulation of lysosomal damage response and autophagy.Journal of molecular medicine (Berlin, Germany) · 2024Review
- Regulation of autophagy gene expression and its implications in cancer.Journal of cell science · 2023Review
- The regulatory mechanism and therapeutic potential of transcription factor EB in neurodegenerative diseases.CNS neuroscience & therapeutics · 2023Review
- Invading Bacterial Pathogens Activate Transcription Factor EB in Epithelial Cells through the Amino Acid Starvation Pathway of mTORC1 Inhibition.Molecular and cellular biology · 2022Article
- Plasmacytoma variant translocation 1 stabilized by EIF4A3 promoted malignant biological behaviors of lung adenocarcinoma by generating circular RNA LMNB2.Bioengineered · 2022Article
- Regulation of Autophagy by the Glycogen Synthase Kinase-3 (GSK-3) Signaling Pathway.International journal of molecular sciences · 2022Review
- The Interplay Between Autophagy and RNA Homeostasis: Implications for Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.Frontiers in cell and developmental biology · 2022Review
- Article
- EIF4A3: a gatekeeper of autophagy.Autophagy · 2021Article
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Authors and funding
10 authors at 4 institutions in 4 countries.
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Abstract
During autophagy, the coordinated actions of autophagosomes and lysosomes result in the controlled removal of damaged intracellular organelles and superfluous substrates. The evolutionary conservation of this process and its requirement for maintaining cellular homeostasis emphasizes the need to better dissect the pathways governing its molecular regulation. In our previously performed high-content screen, we assessed the effect of 1530 RNA-binding proteins on autophagy. Among the top regulators, we identified the eukaryotic translation initiation factor 4A-3 (eIF4A3). Here we show that depletion of eIF4A3 leads to a potent increase in autophagosome and lysosome biogenesis and an enhanced autophagic flux. This is mediated by the key autophagy transcription factor, TFEB, which becomes dephosphorylated and translocates from the cytoplasm to the nucleus where it elicits an integrated transcriptional response. We further identified an exon-skipping event in the transcript encoding for the direct TFEB kinase, GSK3B, which leads to a reduction in GSK3B expression and activity. Through analysis of TCGA data, we found a significant upregulation of eIF4A3 expression across several cancer types and confirmed the potential relevance of this newly identified signaling axis in human tumors. Hence, our data suggest a previously unrecognized role for eIF4A3 as a gatekeeper of autophagy through the control of TFEB activation, revealing a new mechanism for autophagy regulation.
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