ArticleScientific reports2017
Inhibition of the inflammatory response to stress by targeting interaction between PKR and its cellular activator PACT.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- A new approach to discovering a broad-spectrum anti-respiratory virus drug: Tubeimoside II modulates host factor PACT to potentiate the RIG-I antiviral pathway.Acta pharmaceutica Sinica. B · 2026Article
- Cigarette Smoke Induces Canonical Stress Granule Formation in Human Bronchial Epithelial Cells in Reactive Oxygen Species- and PERK-Dependent Manners.Biomolecules · 2026Article
- Article
- IFN alpha inducible protein 27 (IFI27) acts as a positive regulator of PACT-dependent PKR activation after RNA virus infections.PLoS pathogens · 2025Article
- Coronavirus S protein alters dsRNA accumulation and stress granule formation through regulation of ADAR1-p150 expression.Nucleic acids research · 2024Article
- RNA recognition by PKR during DNA virus infection.Journal of medical virology · 2024Review
- Luteolin Is a Potential Immunomodulating Natural Compound against Pulpal Inflammation.BioMed research international · 2024Article
- ISG15/USP18/STAT2 is a molecular hub regulating IFN I-mediated control of Dengue and Zika virus replication.Frontiers in immunology · 2024Article
- Novel Antiviral Molecules against Ebola Virus Infection.International journal of molecular sciences · 2023Article
- The integrated stress response is activated in the salivary glands of Sjögren's syndrome patients.Frontiers in medicine · 2023Article
- Luteolin protects DYT-Frontiers in pharmacology · 2023Article
- The diagnostic and prognostic implications of PRKRA expression in HBV-related hepatocellular carcinoma.Infectious agents and cancer · 2022Article
- A tale of two proteins: PACT and PKR and their roles in inflammation.The FEBS journal · 2021Review
- PKR activity modulation by phosphomimetic mutations of serine residues located three aminoacids upstream of double-stranded RNA binding motifs.Scientific reports · 2021Article
- RETRACTED: Inhibition of anti-viral stress granule formation by coronavirus endoribonuclease nsp15 ensures efficient virus replication.PLoS pathogens · 2021Article
- Inhibition of PKR by Viruses.Frontiers in microbiology · 2021Review
- Dystonia 16 (DYT16) mutations in PACT cause dysregulated PKR activation and eIF2α signaling leading to a compromised stress response.Neurobiology of disease · 2020Article
- Inhibition of RNA-binding proteins with small molecules.Nature reviews. Chemistry · 2020Review
- Article
- Regulation of cGAS-Mediated Immune Responses and Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2020Review
Corrections and comments
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Authors and funding
17 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PKR is a cellular kinase involved in the regulation of the integrative stress response (ISR) and pro-inflammatory pathways. Two N-terminal dsRNA Binding Domains (DRBD) are required for activation of PKR, by interaction with either dsRNA or PACT, another cellular DRBD-containing protein. A role for PKR and PACT in inflammatory processes linked to neurodegenerative diseases has been proposed and raised interest for pharmacological PKR inhibitors. However, the role of PKR in inflammation is subject to controversy. We identified the flavonoid luteolin as an inhibitor of the PKR/PACT interaction at the level of their DRBDs using high-throughput screening of chemical libraries by homogeneous time-resolved fluorescence. This was further validated using NanoLuc-Based Protein Complementation Assay. Luteolin inhibits PKR phosphorylation, the ISR and the induction of pro-inflammatory cytokines in human THP1 macrophages submitted to oxidative stress and toll-like receptor (TLR) agonist. Similarly, luteolin inhibits induction of pro-inflammatory cytokines in murine microglial macrophages. In contrast, luteolin increased activation of the inflammasome, in a PKR-independent manner. Collectively, these data delineate the importance of PKR in the inflammation process to the ISR and induction of pro-inflammatory cytokines. Pharmacological inhibitors of PKR should be used in combination with drugs targeting directly the inflammasome.
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