ArticleNucleic acids research2012
Translation termination efficiency modulates ATF4 response by regulating ATF4 mRNA translation at 5' short ORFs.
Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 39 citations in OpenAlex.
- Article
- ATF4 Coordinates Transcriptomic and Structural Adaptations in Aging Muscle.bioRxiv : the preprint server for biology · 2026Article
- Flexibility and modulation of translation initiation in enterovirus genomes.PLoS pathogens · 2026Article
- Recent Advances in Engineering the Unfolded Protein Response in Recombinant Chinese Hamster Ovary Cell Lines.International journal of molecular sciences · 2025Review
- ATF4 promotes renal tubulointerstitial fibrosis through hexokinase II-mediated glycolysis.Frontiers in immunology · 2025Article
- On the identification of differentially-active transcription factors from ATAC-seq data.PLoS computational biology · 2024Article
- On the identification of differentially-active transcription factors from ATAC-seq data.bioRxiv : the preprint server for biology · 2024Article
- Cell death or survival: Insights into the role of mRNA translational control.Seminars in cell & developmental biology · 2024Review
- Article
- Activating transcription factor 4 regulates hypoxia inducible factor 1α in chronic hypoxia in pancreatic cancer cells.Oncology reports · 2023Article
- UVB-induced eIF2α phosphorylation in keratinocytes depends on decreased ATF4, GADD34 and CReP expression levels.Life sciences · 2021Article
- Article
- Identification of five genes in endoplasmic reticulum (ER) stress-apoptosis pathways in yellow catfish Pelteobagrus fulvidraco and their transcriptional responses to dietary lipid levels.Fish physiology and biochemistry · 2019Article
- Oxidative Stress Triggers Selective tRNA Retrograde Transport in Human Cells during the Integrated Stress Response.Cell reports · 2019Article
- Article
- DDX3 regulates endoplasmic reticulum stress-induced ATF4 expression.Scientific reports · 2017Article
- mTOR regulates the expression of DNA damage response enzymes in long-lived Snell dwarf, GHRKO, and PAPPA-KO mice.Aging cell · 2017Article
- Review
- Nutrient shortage triggers the hexosamine biosynthetic pathway via the GCN2-ATF4 signalling pathway.Scientific reports · 2016Article
- mTORC1 and CK2 coordinate ternary and eIF4F complex assembly.Nature communications · 2016Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The activating transcription factor 4 (ATF4) promotes transcriptional upregulation of specific target genes in response to cellular stress. ATF4 expression is regulated at the translational level by two short open reading frames (uORFs) in its 5'-untranslated region (5'-UTR). Here, we describe a mechanism regulating ATF4 expression in translation termination-deficient human cells. Using microarray analysis of total RNA and polysome-associated mRNAs, we show that depletion of the eucaryotic release factor 3a (eRF3a) induces upregulation of ATF4 and of ATF4 target genes. We show that eRF3a depletion modifies ATF4 translational control at regulatory uORFs increasing ATF4 ORF translation. Finally, we show that the increase of REDD1 expression, one of the upregulated targets of ATF4, is responsible for the mTOR pathway inhibition in eRF3a-depleted cells. Our results shed light on the molecular mechanisms connecting eRF3a depletion to mammalian target of rapamycin (mTOR) pathway inhibition and give an example of ATF4 activation that bypasses the signal transduction cascade leading to the phosphorylation of eIF2α. We propose that in mammals, in which the 5'-UTR regulatory elements of ATF4 mRNA are strictly conserved, variations in translation termination efficiency allow the modulation of the ATF4 response.
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