ArticleNature communications2020
Translational induction of ATF4 during integrated stress response requires noncanonical initiation factors eIF2D and DENR.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 101 citations in OpenAlex.
- Article
- hY3 RNA binds and inhibits ribosomes and modulates the starvation-induced integrated stress response.Nucleic acids research · 2026Article
- The Drosophila CEBPG homolog Irbp18 partners with crc (ATF4) to mediate the integrated stress response in degenerative disease models.Cell reports · 2026Article
- ATF4 Coordinates Transcriptomic and Structural Adaptations in Aging Muscle.bioRxiv : the preprint server for biology · 2026Article
- Mitochondria-associated programmed cell death in pancreatic β cell of T2DM.Apoptosis : an international journal on programmed cell death · 2026Review
- Regulation of Translation of ATF4 mRNA: A Focus on Translation Initiation Factors and RNA-Binding Proteins.Cells · 2026Review
- eIF3d and eIF3e mediate selective translational control of hypoxia that can be inhibited by small molecules.Cell reports · 2025Article
- 4EHP and NELF-E regulate physiological ATF4 induction and proteostasis in disease models of Drosophila.Nature communications · 2025Article
- Review
- eIF2D promotes 40S ribosomal subunit recycling during intrinsic ribosome destabilization.Nucleic acids research · 2025Article
- ATF-4 deficiency increases ER stress and induces osteoarthritis formation in mice.Molecular and cellular biochemistry · 2025Article
- Diverse roles of stress-responsive RNP granules in oogenesis and infertility.Biology of reproduction · 2025Review
- Article
- Unravelling axonal transcriptional landscapes: insights from induced pluripotent stem cell-derived cortical neurons and implications for motor neuron degeneration.Open biology · 2025Article
- eIF3d and eIF3e mediate selective translational control of hypoxia that can be inhibited by novel small molecules.bioRxiv : the preprint server for biology · 2025Article
- Targeting polyunsaturated fatty acids desaturase FADS1 inhibits renal cancer growth via ATF3-mediated ER stress response.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Article
- ADAR1 p150 prevents HSV-1 from triggering PKR/eIF2α-mediated translational arrest and is required for efficient viral replication.PLoS pathogens · 2025Article
- Circadian Control of Protein Synthesis.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- MCTS2 and distinct eIF2D roles in uORF-dependent translation regulation revealed by in vitro re-initiation assays.The EMBO journal · 2025Article
- Distinct Proteomic Brain States Underlying Long-Term Memory Formation in Aversive Operant Conditioning.Journal of proteome research · 2025Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The Integrated Stress Response (ISR) helps metazoan cells adapt to cellular stress by limiting the availability of initiator methionyl-tRNA for translation. Such limiting conditions paradoxically stimulate the translation of ATF4 mRNA through a regulatory 5' leader sequence with multiple upstream Open Reading Frames (uORFs), thereby activating stress-responsive gene expression. Here, we report the identification of two critical regulators of such ATF4 induction, the noncanonical initiation factors eIF2D and DENR. Loss of eIF2D and DENR in Drosophila results in increased vulnerability to amino acid deprivation, susceptibility to retinal degeneration caused by endoplasmic reticulum (ER) stress, and developmental defects similar to ATF4 mutants. eIF2D requires its RNA-binding motif for regulation of 5' leader-mediated ATF4 translation. Consistently, eIF2D and DENR deficient human cells show impaired ATF4 protein induction in response to ER stress. Altogether, our findings indicate that eIF2D and DENR are critical mediators of ATF4 translational induction and stress responses in vivo.
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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.