ArticleThe EMBO journal2017
Protein synthesis inhibition and GADD34 control IFN-β heterogeneous expression in response to dsRNA.
Article in The EMBO journal, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 80 citations in OpenAlex.
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- Single-nuclei UPR profiling by flow cytometry reveals bortezomib resistance mechanisms in multiple myeloma.EMBO molecular medicine · 2026Article
- The assembly of stress granules during foot-and-mouth disease virus infection is uncoupled from activation of cellular intrinsic antiviral signalling.PLoS pathogens · 2026Article
- VPS34-IN1 potentiates STING-dependent activation in human CAL-1 cells.Cellular & molecular biology letters · 2026Article
- Integrative analysis of cuproptosis in kidney ischemia-reperfusion injury: biomarker discovery and diagnostic model construction.Frontiers in molecular biosciences · 2026Article
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- Spring viraemia of carp virus modulates the time-dependent unfolded protein response to facilitate viral replication.Frontiers in immunology · 2025Article
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- SARS-CoV-2 Nucleocapsid Protein Antagonizes GADD34-Mediated Innate Immune Pathway through Atypical Foci.Molecules (Basel, Switzerland) · 2024Article
- A closer look at mammalian antiviral condensates.Biochemical Society transactions · 2024Review
- Endonucleolytic RNA cleavage drives changes in gene expression during the innate immune response.Cell reports · 2024Article
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- Regulation of PKR-dependent RNA translation inhibition by TRIM21 upon virus infection or other stress.PLoS pathogens · 2023Article
- Stress granules are shock absorbers that prevent excessive innate immune responses to dsRNA.Molecular cell · 2023Article
- Nucleic acid-protein condensates in innate immune signaling.The EMBO journal · 2023Review
- Review
- Cellular origins of dsRNA, their recognition and consequences.Nature reviews. Molecular cell biology · 2022Review
- Temporal control of the integrated stress response by a stochastic molecular switch.Science advances · 2022Article
- Genetic Examination of Hematological Parameters in SARS-CoV-2 Infection and COVID-19.medRxiv : the preprint server for health sciences · 2022Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In innate immune responses, induction of type-I interferons (IFNs) prevents virus spreading while viral replication is delayed by protein synthesis inhibition. We asked how cells perform these apparently contradictory activities. Using single fibroblast monitoring by flow cytometry and mathematical modeling, we demonstrate that type-I IFN production is linked to cell's ability to enter dsRNA-activated PKR-dependent translational arrest and then overcome this inhibition by decreasing eIF2α phosphorylation through phosphatase 1c cofactor GADD34 (Ppp1r15a) expression. GADD34 expression, shown here to be dependent on the IRF3 transcription factor, is responsible for a biochemical cycle permitting pulse of IFN synthesis to occur in cells undergoing protein synthesis inhibition. Translation arrest is further demonstrated to be key for anti-viral response by acting synergistically with MAVS activation to amplify TBK1 signaling and IFN-β mRNA transcription, while GADD34-dependent protein synthesis recovery contributes to the heterogeneous expression of IFN observed in dsRNA-activated cells.
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