ArticleNature communications2021
Sugar phosphate activation of the stress sensor eIF2B.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- Allosteric disordering of eIF2B regulates the integrated stress response.Nature chemical biology · 2026Article
- Regulation of RNA-binding proteins by small biomolecules.Nature reviews. Molecular cell biology · 2026Review
- Termination of the integrated stress response.Science (New York, N.Y.) · 2026Article
- Regulation of Translation of ATF4 mRNA: A Focus on Translation Initiation Factors and RNA-Binding Proteins.Cells · 2026Review
- Article
- Chronic integrated stress response causes dysregulated cholesterol synthesis in white matter disease.JCI insight · 2025Article
- The translational landscape of reactive astrocytes reveals the impact of eIF2B-mediated dysregulation in VWM disease.NAR molecular medicine · 2025Article
- Surviving and Adapting to Stress: Translational Control and the Integrated Stress Response.Antioxidants & redox signaling · 2023Review
- Fructose induced KHK-C can increase ER stress independent of its effect on lipogenesis to drive liver disease in diet-induced and genetic models of NAFLD.Metabolism: clinical and experimental · 2023Article
- Protein-metabolite interactomics of carbohydrate metabolism reveal regulation of lactate dehydrogenase.Science (New York, N.Y.) · 2023Article
- Fructose Induced KHK-C Increases ER Stress and Modulates Hepatic Transcriptome to Drive Liver Disease in Diet-Induced and Genetic Models of NAFLD.bioRxiv : the preprint server for biology · 2023Article
- Signaling plasticity in the integrated stress response.Frontiers in cell and developmental biology · 2023Review
- Regulation and function of elF2B in neurological and metabolic disorders.Bioscience reports · 2022Review
- Article
- Understanding emerging bioactive metabolites with putative roles in cancer biology.Frontiers in oncology · 2022Review
- GTP binding to translation factor eIF2B stimulates its guanine nucleotide exchange activity.iScience · 2021Article
- Elucidation of the Translation Initiation Factor Interaction Network ofFrontiers in microbiology · 2021Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
Abstract
The multi-subunit translation initiation factor eIF2B is a control node for protein synthesis. eIF2B activity is canonically modulated through stress-responsive phosphorylation of its substrate eIF2. The eIF2B regulatory subcomplex is evolutionarily related to sugar-metabolizing enzymes, but the biological relevance of this relationship was unknown. To identify natural ligands that might regulate eIF2B, we conduct unbiased binding- and activity-based screens followed by structural studies. We find that sugar phosphates occupy the ancestral catalytic site in the eIF2Bα subunit, promote eIF2B holoenzyme formation and enhance enzymatic activity towards eIF2. A mutant in the eIF2Bα ligand pocket that causes Vanishing White Matter disease fails to engage and is not stimulated by sugar phosphates. These data underscore the importance of allosteric metabolite modulation for proper eIF2B function. We propose that eIF2B evolved to couple nutrient status via sugar phosphate sensing with the rate of protein synthesis, one of the most energetically costly cellular processes.
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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.