ArticleScience (New York, N.Y.)2015
Stress responses. Mutations in a translation initiation factor identify the target of a memory-enhancing compound.
Article in Science (New York, N.Y.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
141 citing papers in PubMed, 232 citations in OpenAlex.
- Allosteric disordering of eIF2B regulates the integrated stress response.Nature chemical biology · 2026Article
- Metabolite import by SLC33A1 is required for ATF6 activation during endoplasmic reticulum stress.Life science alliance · 2026Article
- A molecular stabiliser of an inhibitory eIF2B-eIF2(αP) complex activates the Integrated Stress Response.Nature communications · 2026Article
- Zinc accumulation-induced integrated stress response triggers β-cell identity loss.Cell research · 2026Article
- The Art of Domesticating Proteins: How Cancer Cells Adapt to Therapeutic and Environmental Stressors.International journal of molecular sciences · 2026Review
- Directional Modulation of the Integrated Stress Response in Neurodegeneration: A Systematic Review of eIF2B Activators, PERK-Pathway Agents, and ISR Prolongers.Biomedicines · 2026Review
- The strategies and advances of mRNA translation booster.Asian journal of pharmaceutical sciences · 2025Review
- EIF2B4 promotes hepatocellular carcinoma progression and immune evasion by driving STAT3 translation via a GEF-dependent mechanism.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Navigating the landscape of protein folding and proteostasis: from molecular chaperones to therapeutic innovations.Signal transduction and targeted therapy · 2025Review
- The Integrated Stress Response Pathway Coordinates Translational Control of Multiple Immune Checkpoints in Lung Cancer.Cancer research · 2025Article
- Signal transduction pathways controllingiScience · 2025Article
- Effects of acute pro-inflammatory stimulation and 25-hydroxycholesterol on hippocampal plasticity and learning involve NLRP3 inflammasome and cellular stress responses.Scientific reports · 2025Article
- The integrated stress response in neurodegenerative diseases.Molecular neurodegeneration · 2025Review
- Maximizing ISRIB Potential Requires Addressing Specificity, Long-term Safety, and Disease-specific Considerations.Current medicinal chemistry · 2025Review
- Sertraline modulates hippocampal plasticity via sigma 1 receptors, cellular stress and neurosteroids.Translational psychiatry · 2024Article
- Article
- Defective regulation of the eIF2-eIF2B translational axis underlies depressive-like behavior in mice and correlates with major depressive disorder in humans.Translational psychiatry · 2024Article
- Molecular glues for protein-protein interactions: Progressing toward a new dream.Cell chemical biology · 2024Review
- Mammalian integrated stress responses in stressed organelles and their functions.Acta pharmacologica Sinica · 2024Review
- Mammalian integrated stress responses in stressed organelles and their functions.Acta pharmacologica Sinica · 2024Review
81 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The integrated stress response (ISR) modulates messenger RNA translation to regulate the mammalian unfolded protein response (UPR), immunity, and memory formation. A chemical ISR inhibitor, ISRIB, enhances cognitive function and modulates the UPR in vivo. To explore mechanisms involved in ISRIB action, we screened cultured mammalian cells for somatic mutations that reversed its effect on the ISR. Clustered missense mutations were found at the amino-terminal portion of the delta subunit of guanine nucleotide exchange factor (GEF) eIF2B. When reintroduced by CRISPR-Cas9 gene editing of wild-type cells, these mutations reversed both ISRIB-mediated inhibition of the ISR and its stimulatory effect on eIF2B GEF activity toward its substrate, the translation initiation factor eIF2, in vitro. Thus, ISRIB targets an interaction between eIF2 and eIF2B that lies at the core of the ISR.
Indexed as
Identifiers
What OpenQuestion holds
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.