ArticleScience advances2020
GADD34 is a modulator of autophagy during starvation.
Article in Science advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 61 citations in OpenAlex.
- Revisiting Inherited Metabolic Diseases (IMDs) Through the Lens of Selective Autophagy.Journal of inherited metabolic disease · 2026Review
- Melatonin Regulates Growth-Arrest and DNA-Damage Genes GADD153, GADD45g and GADD34 in Experimental Varicocele.Cell biochemistry and function · 2026Article
- Protein Palmitoylation as a Molecular Switch Linking Regulated Cell Death and Disease.Biomolecules · 2026Review
- The redundant protein synthesis gene Aimp1 challenges the canonical inverse relationship between translation and autophagy.Communications biology · 2026Article
- Multi-Omic, Multi-Tissue Responses to Acute Exercise in Sedentary Adults: Findings from the Molecular Transducers of Physical Activity Consortium.bioRxiv : the preprint server for biology · 2026Article
- TFEB coordinates autophagosome biogenesis and ribophagy during starvation via SQSTM1.Science advances · 2026Article
- RNA-mediated condensation of TFE3 oncofusions facilitates transcriptional hub formation to promote translocation renal cell carcinoma.Nature communications · 2025Article
- A longevity-associated variant of the human BPIFB4 gene prevents diastolic dysfunction in progeria mice.Signal transduction and targeted therapy · 2025Article
- Amyotrophic Lateral Sclerosis: Focus on Cytoplasmic Trafficking and Proteostasis.Molecular neurobiology · 2025Review
- Leucine aminopeptidase LyLAP enables lysosomal degradation of membrane proteins.Science (New York, N.Y.) · 2025Article
- Multilevel plasticity and altered glycosylation drive aggressiveness in hypoxic and glucose-deprived bladder cancer cells.iScience · 2025Article
- Protein phosphatase 1 regulatory subunit 15 A (PPP1R15A) promoted the progression of gastric cancer by activating cell autophagy under energy stress.Journal of experimental & clinical cancer research : CR · 2025Article
- GADD45α is a direct target of TFEB and contributes to tacrolimus-induced chronic nephrotoxicity.JCI insight · 2025Article
- Modulation of Autophagy by Oncosuppressor FAM46C and Its Implications for Cancer Therapy: An Intriguing Perspective.Biomolecules · 2025Review
- Comprehensive Analysis of Programmed Cell Death-Related Genes in Diagnosis and Synovitis During Osteoarthritis Development: Based on Bulk and Single-Cell RNA Sequencing Data.Journal of inflammation research · 2025Article
- Mechanisms and cross-talk of regulated cell death and their epigenetic modifications in tumor progression.Molecular cancer · 2024Review
- Integrative Bioinformatics Analysis Reveals a Transcription Factor EB-Driven MicroRNA Regulatory Network in Endothelial Cells.International journal of molecular sciences · 2024Article
- Mammalian integrated stress responses in stressed organelles and their functions.Acta pharmacologica Sinica · 2024Review
- A single dose of cocaine rewires the 3D genome structure of midbrain dopamine neurons.bioRxiv : the preprint server for biology · 2024Article
- Human Betacoronavirus OC43 Interferes with the Integrated Stress Response Pathway in Infected Cells.Viruses · 2024Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cells respond to starvation by shutting down protein synthesis and by activating catabolic processes, including autophagy, to recycle nutrients. This two-pronged response is mediated by the integrated stress response (ISR) through phosphorylation of eIF2α, which represses protein translation, and by inhibition of mTORC1 signaling, which promotes autophagy also through a stress-responsive transcriptional program. Implementation of such a program, however, requires protein synthesis, thus conflicting with general repression of translation. How is this mismatch resolved? We found that the main regulator of the starvation-induced transcriptional program, TFEB, counteracts protein synthesis inhibition by directly activating expression of GADD34, a component of the protein phosphatase 1 complex that dephosphorylates eIF2α. We discovered that GADD34 plays an essential role in autophagy by tuning translation during starvation, thus enabling lysosomal biogenesis and a sustained autophagic flux. Hence, the TFEB-GADD34 axis integrates the mTORC1 and ISR pathways in response to starvation.
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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.