ArticleScience advances2022
Temporal control of the integrated stress response by a stochastic molecular switch.
Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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Who cites it
27 citing papers in PubMed, 53 citations in OpenAlex.
- EPHA2/CD44-directed trafficking enhances endosomal leakiness and antisense therapy delivery.The Journal of cell biology · 2026Article
- The Role of Long Noncoding RNAs in Modulation of Stress Granules in Cancer.Journal of cellular and molecular medicine · 2026Review
- Stress granule phase separation in stress-responsive cytosolic extract-in-oil droplets.Nature communications · 2026Article
- The Janus framework of the integrated stress response: from homeostasis to maladaptation.Life science alliance · 2026Review
- Review
- In vivo modeling of lethal congenital contracture syndrome 1 suggests pathomechanisms in cellular stress responses.The FEBS journal · 2025Article
- Systems Virology at Scale.Current opinion in systems biology · 2025Article
- Intramolecular competition generates pulsatory protein activity shaped by light, temperature, and evolution.bioRxiv : the preprint server for biology · 2025Article
- Drug-tolerant persister cells in cancer: bridging the gaps between bench and bedside.Nature communications · 2025Review
- Article
- Induction of Stress Granules and Developmental Instability of Offspring Phenotype Due to Hypothermia During First Mouse Embryo Cleavage.International journal of molecular sciences · 2025Article
- Dual Nature of Mitochondrial Integrated Stress Response: Molecular Switches from Protection to Pathology.Genes · 2025Review
- Metabolic traits shape responses to LSD1-directed therapy in glioblastoma tumor-initiating cells.Science advances · 2025Article
- Article
- Homeostasis control in health and disease by the unfolded protein response.Nature reviews. Molecular cell biology · 2025Review
- The integrated stress response engages a cell-autonomous, ligand-independent, DR5-driven apoptosis switch.Cell death & disease · 2025Article
- Mapping the Genetic Architecture of the Adaptive Integrated Stress Response inbioRxiv : the preprint server for biology · 2024Article
- Translation regulation in response to stress.The FEBS journal · 2024Review
- SARS-CoV-2 Nucleocapsid Protein Antagonizes GADD34-Mediated Innate Immune Pathway through Atypical Foci.Molecules (Basel, Switzerland) · 2024Article
- eIF2B localization and its regulation during the integrated stress response is cell-type specific.iScience · 2024Article
Corrections and comments
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Authors and funding
21 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stress granules (SGs) are formed in the cytosol as an acute response to environmental cues and activation of the integrated stress response (ISR), a central signaling pathway controlling protein synthesis. Using chronic virus infection as stress model, we previously uncovered a unique temporal control of the ISR resulting in recurrent phases of SG assembly and disassembly. Here, we elucidate the molecular network generating this fluctuating stress response by integrating quantitative experiments with mathematical modeling and find that the ISR operates as a stochastic switch. Key elements controlling this switch are the cooperative activation of the stress-sensing kinase PKR, the ultrasensitive response of SG formation to the phosphorylation of the translation initiation factor eIF2α, and negative feedback via GADD34, a stress-induced subunit of protein phosphatase 1. We identify GADD34 messenger RNA levels as the molecular memory of the ISR that plays a central role in cell adaptation to acute and chronic stress.
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.