ArticleeLife2021
eIF2B conformation and assembly state regulate the integrated stress response.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 50 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.
- ER stress as a trigger of UPR and ER-phagy in cancer growth and spread.Frontiers in oncology · 2022Pooled it
- Structural Transformation of a BRAF Inhibitor into a Selective PKR Inhibitor.Journal of medicinal chemistry · 2026Article
- Allosteric disordering of eIF2B regulates the integrated stress response.Nature chemical biology · 2026Article
- A molecular stabiliser of an inhibitory eIF2B-eIF2(αP) complex activates the Integrated Stress Response.Nature communications · 2026Article
- Regulation of Translation of ATF4 mRNA: A Focus on Translation Initiation Factors and RNA-Binding Proteins.Cells · 2026Review
- Prime editing links the split integrated stress response to pathogenic eIF2B mutations and white matter degeneration.Cell death & disease · 2025Article
- Pharmacological targeting of RIG-I can selectively activate the integrated stress response.Science advances · 2025Article
- Raphin-1 mediates the survival and sensitivity to radiation of pediatric-type diffuse high-grade glioma via phosphorylated eukaryotic initiation factor 2α-dependent and -independent processes.Molecular oncology · 2025Article
- Chronic integrated stress response causes dysregulated cholesterol synthesis in white matter disease.JCI insight · 2025Article
- Homeostasis control in health and disease by the unfolded protein response.Nature reviews. Molecular cell biology · 2025Review
- The Translation Initiation Factor eIF2Bα Regulates Development, Stress Response, Amylase Production, and Kojic Acid Synthesis in the Fungus Aspergillus oryzae.Current microbiology · 2025Review
- Maximizing ISRIB Potential Requires Addressing Specificity, Long-term Safety, and Disease-specific Considerations.Current medicinal chemistry · 2025Review
- Specific activation of the integrated stress response uncovers regulation of central carbon metabolism and lipid droplet biogenesis.Nature communications · 2024Article
- eIF2B localization and its regulation during the integrated stress response is cell-type specific.iScience · 2024Article
- Article
- O-GlcNAcylation of MITF regulates its activity and CDK4/6 inhibitor resistance in breast cancer.Nature communications · 2024Article
- Functional transcriptome analysis revealed major changes in pathways affecting systems biology of Tharparkar cattle under seasonal heat stress.3 Biotech · 2024Article
- Reversal of pulmonary veno-occlusive disease phenotypes by inhibition of the integrated stress response.Nature cardiovascular research · 2024Article
- Molecular glues for protein-protein interactions: Progressing toward a new dream.Cell chemical biology · 2024Review
- Evaluation of safety and early efficacy of AAV gene therapy in mouse models of vanishing white matter disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The integrated stress response (ISR) is activated by phosphorylation of the translation initiation factor eIF2 in response to various stress conditions. Phosphorylated eIF2 (eIF2-P) inhibits eIF2's nucleotide exchange factor eIF2B, a twofold symmetric heterodecamer assembled from subcomplexes. Here, we monitor and manipulate eIF2B assembly in vitro and in vivo. In the absence of eIF2B's α-subunit, the ISR is induced because unassembled eIF2B tetramer subcomplexes accumulate in cells. Upon addition of the small-molecule ISR inhibitor ISRIB, eIF2B tetramers assemble into active octamers. Surprisingly, ISRIB inhibits the ISR even in the context of fully assembled eIF2B decamers, revealing allosteric communication between the physically distant eIF2, eIF2-P, and ISRIB binding sites. Cryo-electron microscopy structures suggest a rocking motion in eIF2B that couples these binding sites. eIF2-P binding converts eIF2B decamers into 'conjoined tetramers' with diminished substrate binding and enzymatic activity. Canonical eIF2-P-driven ISR activation thus arises due to this change in eIF2B's conformational state.
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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.