ArticleMolecular cell2017
A Unique ISR Program Determines Cellular Responses to Chronic Stress.
Article in Molecular cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 papers.
What it found
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Who cites it
133 citing papers in PubMed, 201 citations in OpenAlex.
- Review
- The mitochondrial unfolded protein response in human microglia disrupts neuronal-glial communication and promotes senescence.Nature neuroscience · 2026Article
- Elongationless start-stop elements are stress-resilient translation gates that are more repressive than uTranslons.Nucleic acids research · 2026Article
- Inhibition of the mitochondrial pyruvate carrier attenuates the integrated stress response activation in a cellular model of Huntington's disease.Molecular and cellular biochemistry · 2026Article
- Genomic insights into the tunicamycin-induced endoplasmic reticulum stress response in peripheral blood mononuclear cells: A comprehensive RNA sequencing analysis.Biochemistry and biophysics reports · 2026Article
- Enhancement of Therapeutic mRNA Translation in Cellular Stress Conditions.International journal of molecular sciences · 2026Review
- CHOP promotes the transition to chronic integrated stress response signaling with suppression of hepatocyte identity.bioRxiv : the preprint server for biology · 2026Article
- Pde4 mediates MHCII expression in oligodendroglia.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The integrated stress response in cancer: mechanisms of tumor adaptation and therapeutic targeting.Biochemical Society transactions · 2026Review
- Metabolic adaptation to IMMT deficiency through the ATF6-PPARγ axis is contingent on TP53 mutation status in breast cancer.Cell death & disease · 2026Article
- Posttranscriptional reprogramming controls MASLD progression through chronic ER stress adaptation.Science advances · 2026Article
- Deficiency of PTEN Confers Hypersensitivity to Fatty Acid-Mediated ER Stress in Transformed Hepatocytes.International journal of molecular sciences · 2026Article
- The Janus framework of the integrated stress response: from homeostasis to maladaptation.Life science alliance · 2026Review
- Decoding the Integrated Stress Response of Pancreatic Cancer: Identifying a Serine-dependent Tumor Subset Under Metabolic Relationships With CAFs.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Regulation of Translation of ATF4 mRNA: A Focus on Translation Initiation Factors and RNA-Binding Proteins.Cells · 2026Review
- Inhibition of the integrated stress response rescues a histidyl-tRNA synthetase variant associated with Charcot-Marie-Tooth disease.NAR molecular medicine · 2026Article
- eIF3d and eIF3e mediate selective translational control of hypoxia that can be inhibited by small molecules.Cell reports · 2025Article
- Space radiation induces distinct senescent phenotypes: Implications for space travel.npj aging · 2025Article
- DDX3X acts as a selective dual switch regulator of mRNA translation in acute ER stress.Cell reports · 2025Article
- Epigenetic alterations facilitate transcriptional and translational programs in hypoxia.Nature cell biology · 2025Article
73 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 8 institutions in 5 countries.
Funding
Abstract
The integrated stress response (ISR) is a homeostatic mechanism induced by endoplasmic reticulum (ER) stress. In acute/transient ER stress, decreased global protein synthesis and increased uORF mRNA translation are followed by normalization of protein synthesis. Here, we report a dramatically different response during chronic ER stress. This chronic ISR program is characterized by persistently elevated uORF mRNA translation and concurrent gene expression reprogramming, which permits simultaneous stress sensing and proteostasis. The program includes PERK-dependent switching to an eIF3-dependent translation initiation mechanism, resulting in partial, but not complete, translational recovery, which, together with transcriptional reprogramming, selectively bolsters expression of proteins with ER functions. Coordination of transcriptional and translational reprogramming prevents ER dysfunction and inhibits "foamy cell" development, thus establishing a molecular basis for understanding human diseases associated with ER dysfunction.
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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.