ArticleThe Journal of cell biology2017
4E-BP is a target of the GCN2-ATF4 pathway during Drosophila development and aging.
Article in The Journal of cell biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 104 citations in OpenAlex.
- Bruno 1 remodels P-bodies to protect select mRNAs during the early ER stress response.Life science alliance · 2026Article
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- The hallmarks of protein and amino acid restriction in aging and longevity.Cell press blue · 2026Article
- The Drosophila CEBPG homolog Irbp18 partners with crc (ATF4) to mediate the integrated stress response in degenerative disease models.Cell reports · 2026Article
- Sexually dimorphic ATF4 expression in the fat confers female stress tolerance in Drosophila melanogaster.Genetics · 2026Article
- Suppression rather than activation of the integrated stress response (GCN2-ATF4) pathway extends lifespan in the fly.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Ring canals in the larval adipose of Drosophila buffer stress response.The Journal of cell biology · 2026Article
- ATF4-dependent upregulation of Bruno 1 remodels P-bodies to selectively protect mRNAs during ER stress throughoutbioRxiv : the preprint server for biology · 2026Article
- 4EHP and NELF-E regulate physiological ATF4 induction and proteostasis in disease models of Drosophila.Nature communications · 2025Article
- Imaginal discs produce neuropeptide-like precursor 1 to alleviate ER stress in response to warm temperatures.Communications biology · 2025Article
- Decanoic acid extends lifespan and modulates metabolism in models of PLA2G6-associated neurodegeneration.Disease models & mechanisms · 2025Article
- The integrated stress response suppresses antiviral RNA interference by autophagy-mediated degradation of the RNA-induced silencing complex.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Emerging roles for integrated stress response signaling in homeostasis.The FEBS journal · 2025Review
- Genetic perturbation of cellular homeostasis regulates integrated stress response signaling to control Drosophila hematopoiesis.Biology open · 2025Article
- Diverse roles of stress-responsive RNP granules in oogenesis and infertility.Biology of reproduction · 2025Review
- Drosophila ubiquitin-specific peptidase 14 stabilizes the PERIOD protein by regulating a ubiquitin ligase SLIMB.Communications biology · 2025Article
- Gap junctions allow transfer of metabolites between germ cells and somatic cells to promote germ cell growth in the Drosophila ovary.PLoS biology · 2025Article
- Sensory quiescence induces a cell-non-autonomous integrated stress response curbed by condensate formation of the ATF4 and XRP1 effectors.Nature communications · 2025Article
- The mitochondrial aspartate transporter Ucp4a regulates muscle aging and animal lifespan in Drosophila melanogaster.PloS one · 2025Article
11 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Reduced amino acid availability attenuates mRNA translation in cells and helps to extend lifespan in model organisms. The amino acid deprivation-activated kinase GCN2 mediates this response in part by phosphorylating eIF2α. In addition, the cap-dependent translational inhibitor 4E-BP is transcriptionally induced to extend lifespan in Drosophila melanogaster, but through an unclear mechanism. Here, we show that GCN2 and its downstream transcription factor, ATF4, mediate 4E-BP induction, and GCN2 is required for lifespan extension in response to dietary restriction of amino acids. The 4E-BP intron contains ATF4-binding sites that not only respond to stress but also show inherent ATF4 activity during normal development. Analysis of the newly synthesized proteome through metabolic labeling combined with click chemistry shows that certain stress-responsive proteins are resistant to inhibition by 4E-BP, and gcn2 mutant flies have reduced levels of stress-responsive protein synthesis. These results indicate that GCN2 and ATF4 are important regulators of 4E-BP transcription during normal development and aging.
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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.