ArticleThe Journal of biological chemistry2012
Protein kinase PKR amplification of interferon β induction occurs through initiation factor eIF-2α-mediated translational control.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.
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Who cites it
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.
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- Differential assembly of RNP granules via activation of distinct dsRNA sensors by adenovirus mutants.bioRxiv : the preprint server for biology · 2026Article
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- Poxvirus K3 Orthologs Regulate NF-κB-Dependent Inflammatory Responses by Targeting the PKR-eIF2α Axis in Multiple Species.Vaccines · 2025Article
- Induction of the ISR by AB5 subtilase cytotoxin drives type-I IFN expression in pDCs via STING activation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Mitigation of 3.5 GHz Electromagnetic Field-Induced BV2 Microglial Cytotoxicity by Polydeoxyribonucleotide.Current issues in molecular biology · 2025Article
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- The monkeypox virus-host interplays.Cell insight · 2024Review
- Crosstalk between vault RNAs and innate immunity.Molecular biology reports · 2024Review
- Nucleic acid-induced inflammation on hematopoietic stem cells.Experimental hematology · 2024Article
- Loss of ADAR1 in macrophages in combination with interferon gamma suppresses tumor growth by remodeling the tumor microenvironment.Journal for immunotherapy of cancer · 2023Article
- Immunomodulatory Role of Interferons in Viral and Bacterial Infections.International journal of molecular sciences · 2023Review
- Stress granules are shock absorbers that prevent excessive innate immune responses to dsRNA.Molecular cell · 2023Article
- Review
- Foot-and-Mouth Disease Virus: Molecular Interplays with IFN Response and the Importance of the Model.Viruses · 2022Review
4 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The protein kinase PKR is activated by RNA with double-stranded (ds) structure and subsequently impairs translation through phosphorylation of protein synthesis initiation factor eIF-2α. PKR also mediates activation of signal transduction pathways leading to interferon beta (IFN-β) gene induction following virus-infection or RNA transfection. We previously demonstrated in measles virus-infected cells that PKR is required for the maximal induction of IFN-β gene expression by the interferon promoter stimulator gene 1 (IPS-1) adaptor-dependent cytosolic RNA sensor pathway. While both IPS-1 and PKR are important mediators of IFN-β induction, with PKR contributing to an enhanced NF-κB activation, the mechanism by which PKR enhances NF-κB activity and amplifies IFN-β induction is unresolved. Herein we tested the possibility that PKR could activate signal transduction pathways indirectly through translational control responses. Following transfection with synthetic or natural dsRNAs or infection with measles virus, we observed increased mRNA but decreased protein levels for the inhibitor of NF-κB signaling, IκB-α, that correlated with PKR activation and eIF-2α phosphorylation. Importantly, knockdown of PKR increased IκB-α protein levels and impaired IFN-β induction. Additionally, inhibition of translation by cycloheximide treatment rescued IFN-β induction following PKR knockdown but not IPS-1 knockdown. Mutation of eIF-2α to prevent phosphorylation also impaired IFN-β induction in PKR-sufficient virus-infected cells. These results suggest that an eIF-2α-dependent translation inhibition mechanism is sufficient to explain the PKR-mediated amplification of IPS-1-dependent IFN-β induction by foreign RNA.
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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.