ArticleNature chemical biology2013
Chemical genetics reveals a kinase-independent role for protein kinase R in pyroptosis.
Article in Nature chemical biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 77 citations in OpenAlex.
- Structural Transformation of a BRAF Inhibitor into a Selective PKR Inhibitor.Journal of medicinal chemistry · 2026Article
- Deciphering the multifaceted role of double-stranded RNA sensor protein kinase R: pathophysiological function beyond the antiviral response.RNA biology · 2025Review
- RNA recognition by PKR during DNA virus infection.Journal of medical virology · 2024Review
- Connexin 43 and Pannexin 1 hemichannels as endogenous regulators of innate immunity in sepsis.Frontiers in immunology · 2024Review
- Aquaporin5 Deficiency Aggravates ROS/NLRP3 Inflammasome-Mediated Pyroptosis in the Lacrimal Glands.Investigative ophthalmology & visual science · 2023Article
- Article
- UBR5 promotes tumor immune evasion through enhancing IFN-γ-inducedTheranostics · 2022Article
- PHOrming the inflammasome: phosphorylation is a critical switch in inflammasome signalling.Biochemical Society transactions · 2021Review
- A tale of two proteins: PACT and PKR and their roles in inflammation.The FEBS journal · 2021Review
- Abortive HIV-1 RNA induces pro-IL-1β maturation via protein kinase PKR and inflammasome activation in humans.European journal of immunology · 2021Article
- Gasdermin D in pyroptosis.Acta pharmaceutica Sinica. B · 2021Review
- Review
- Relevant mediators involved in and therapies targeting the inflammatory response induced by activation of the NLRP3 inflammasome in ischemic stroke.Journal of neuroinflammation · 2021Review
- Molecular insights into the therapeutic promise of targeting HMGB1 in depression.Pharmacological reports : PR · 2021Review
- Protein Kinase R in Bacterial Infections: Friend or Foe?Frontiers in immunology · 2021Review
- Double-Stranded RNA Dependent Kinase R Regulates Antibacterial Immunity in Sepsis.Journal of innate immunity · 2021Article
- The Role of Protein Tyrosine Phosphatases in Inflammasome Activation.International journal of molecular sciences · 2020Review
- Blocking GSDMD processing in innate immune cells but not in hepatocytes protects hepatic ischemia-reperfusion injury.Cell death & disease · 2020Article
- Article
- Peroxynitrite/PKR Axis Modulates the NLRP3 Inflammasome of Cardiac Fibroblasts.Frontiers in immunology · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
Formation of the inflammasome, a scaffolding complex that activates caspase-1, is important in numerous diseases. Pyroptotic cell death induced by anthrax lethal toxin (LT) is a model for inflammasome-mediated caspase-1 activation. We discovered 7-desacetoxy-6,7-dehydrogedunin (7DG) in a phenotypic screen as a small molecule that protects macrophages from LT-induced death. Using chemical proteomics, we identified protein kinase R (PKR) as the target of 7DG and show that RNAi knockdown of PKR phenocopies treatment with 7DG. Further, we show that PKR's role in ASC assembly and caspase-1 activation induced by several different inflammasome stimuli is independent of PKR's kinase activity, demonstrating that PKR has a previously uncharacterized role in caspase-1 activation and pyroptosis that is distinct from its reported kinase-dependent roles in apoptosis and inflammasome formation in lipopolysaccharide-primed cells. Remarkably, PKR has different roles in two distinct cell death pathways and has a broad role in inflammasome function relevant in other diseases.
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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.