ArticleeLife2015
Pharmacological dimerization and activation of the exchange factor eIF2B antagonizes the integrated stress response.
Article in eLife, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 161 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
161 citing papers in PubMed, 260 citations in OpenAlex.
- Investigational eIF2B activator DNL343 modulates the integrated stress response in preclinical models of TDP-43 pathology and individuals with ALS in a randomized clinical trial.Nature communications · 2025Trial
- Avobenzone induces intestinal injury by targeting ATG14 and impairing mitophagy.Cell communication and signaling : CCS · 2026Article
- Unfolding Resilience: Molecular Integration of the Integrated Stress Response and Mitochondrial UPR in Skeletal Muscle Homeostasis.Muscles (Basel, Switzerland) · 2026Review
- The integrated stress response suppresses PINK1-dependent mitophagy by preserving mitochondrial import efficiency.Nature communications · 2026Article
- PERK inhibition attenuates multi-program cell death through Nrf2/HO-1 activation in diabetic retinopathy with integrated proteomics and functional validation in HRECs.Scientific reports · 2026Article
- Adaptive inter-tissue proteostasis networks in aging and neurodegeneration.Bioscience reports · 2026Review
- The integrated stress response in pancreatic β-cell failure in diabetes: from molecular mechanisms to precision therapeutics.Frontiers in endocrinology · 2026Review
- Integrated stress response inhibition prolongs the lifespan of a Pelizaeus-Merzbacher disease mouse model by increasing oligodendrocyte survival.Nature communications · 2025Article
- Review
- Overcoming the eIF2α Brake in Human Cell-Derived Translation Systems.bioRxiv : the preprint server for biology · 2025Article
- Drug repurposing screen identifies an HRI activating compound that promotes adaptive mitochondrial remodeling in MFN2-deficient cells.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- EIF2B4 promotes hepatocellular carcinoma progression and immune evasion by driving STAT3 translation via a GEF-dependent mechanism.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Dual Nature of Mitochondrial Integrated Stress Response: Molecular Switches from Protection to Pathology.Genes · 2025Review
- Drug Repurposing Screen Identifies an HRI Activating Compound that Promotes Adaptive Mitochondrial Remodeling in MFN2-deficient Cells.bioRxiv : the preprint server for biology · 2025Article
- HRI protein kinase in cytoplasmic heme sensing and mitochondrial stress response: Relevance to hematological and mitochondrial diseases.The Journal of biological chemistry · 2025Review
- Homeostasis control in health and disease by the unfolded protein response.Nature reviews. Molecular cell biology · 2025Review
- Article
- ONC213: a novel strategy to resensitize resistant AML cells to venetoclax through induction of mitochondrial stress.Journal of experimental & clinical cancer research : CR · 2025Article
- Peroxisomal import stress activates integrated stress response and inhibits ribosome biogenesis.PNAS nexus · 2024Article
- Specific activation of the integrated stress response uncovers regulation of central carbon metabolism and lipid droplet biogenesis.Nature communications · 2024Article
101 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 4 institutions in 1 country.
Funding
Abstract
The general translation initiation factor eIF2 is a major translational control point. Multiple signaling pathways in the integrated stress response phosphorylate eIF2 serine-51, inhibiting nucleotide exchange by eIF2B. ISRIB, a potent drug-like small molecule, renders cells insensitive to eIF2α phosphorylation and enhances cognitive function in rodents by blocking long-term depression. ISRIB was identified in a phenotypic cell-based screen, and its mechanism of action remained unknown. We now report that ISRIB is an activator of eIF2B. Our reporter-based shRNA screen revealed an eIF2B requirement for ISRIB activity. Our results define ISRIB as a symmetric molecule, show ISRIB-mediated stabilization of activated eIF2B dimers, and suggest that eIF2B4 (δ-subunit) contributes to the ISRIB binding site. We also developed new ISRIB analogs, improving its EC50 to 600 pM in cell culture. By modulating eIF2B function, ISRIB promises to be an invaluable tool in proof-of-principle studies aiming to ameliorate cognitive defects resulting from neurodegenerative diseases.
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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.