ArticleNature cell biology2013
ER-stress-induced transcriptional regulation increases protein synthesis leading to cell death.
Article in Nature cell biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1,077 papers.
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Who cites it
1,077 citing papers in PubMed, 1,664 citations in OpenAlex.
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- Serine Starvation Modulates mRNA Splicing through Translational Inhibition of SRSF Proteins.Cancer research · 2026Article
- Chemical induction and reversal of photoreceptor dystrophy in retinal organoids.Stem cell reports · 2026Article
- Temporal gating dictates stress-induced transcript export from the nucleus.Genes & development · 2026Article
- CReP-mediated control of eIF2α phosphorylation is a critical node in MYC-driven medulloblastoma.Nature communications · 2026Article
- Dissecting the cell biology of the ISR in cognitive disorders at the single-cell resolution.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- "Radiation-Synthesized Gallotannin Hydrogel Attenuates Trisenox-Induced Nephrotoxicity in Rats: miR-223/TXNIP Axis Modulation of Oxidative Stress and Inflammation".Biological trace element research · 2026Article
- GCN2 in proteostasis: structural logic, signalling networks and disease.The FEBS journal · 2026Review
- A multilayered stress-response circuit: The mammalian mitochondrial UPR.The FEBS journal · 2026Review
- The role of ATF4 in neurons under mitochondrial stress.NAR genomics and bioinformatics · 2026Article
- Metabolomics Effects of Folding Correction in Retinitis Pigmentosa Rhodopsin Mutant P23A.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Heat stress reveals bidirectional cross talk between the heat shock response and UPRER in C. elegans.G3 (Bethesda, Md.) · 2026Article
- A Novel Pak1 Activator Ameliorates ER Stress for HFpEF Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Two stress-responsive kinases suppress ferroptosis by activating antioxidant programs under mild oxidative stress.Signal transduction and targeted therapy · 2026Article
- tRNA-derived small RNAs in ocular neovascular diseases: A systematic review.Non-coding RNA research · 2026Review
- Single-nuclei UPR profiling by flow cytometry reveals bortezomib resistance mechanisms in multiple myeloma.EMBO molecular medicine · 2026Article
1,017 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
Protein misfolding in the endoplasmic reticulum (ER) leads to cell death through PERK-mediated phosphorylation of eIF2α, although the mechanism is not understood. ChIP-seq and mRNA-seq of activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP), key transcription factors downstream of p-eIF2α, demonstrated that they interact to directly induce genes encoding protein synthesis and the unfolded protein response, but not apoptosis. Forced expression of ATF4 and CHOP increased protein synthesis and caused ATP depletion, oxidative stress and cell death. The increased protein synthesis and oxidative stress were necessary signals for cell death. We show that eIF2α-phosphorylation-attenuated protein synthesis, and not Atf4 mRNA translation, promotes cell survival. These results show that transcriptional induction through ATF4 and CHOP increases protein synthesis leading to oxidative stress and cell death. The findings suggest that limiting protein synthesis will be therapeutic for diseases caused by protein misfolding in the ER.
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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.