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| Home > Publications Database > Chemical genetics reveals a kinase-independent role for protein kinase R in pyroptosis. > print |
| 001 | 136920 | ||
| 005 | 20240321220147.0 | ||
| 024 | 7 | _ | |a 10.1038/nchembio.1236 |2 doi |
| 024 | 7 | _ | |a pmid:23603659 |2 pmid |
| 024 | 7 | _ | |a pmc:PMC6615456 |2 pmc |
| 024 | 7 | _ | |a 1552-4450 |2 ISSN |
| 024 | 7 | _ | |a 1552-4469 |2 ISSN |
| 024 | 7 | _ | |a altmetric:1404247 |2 altmetric |
| 037 | _ | _ | |a DZNE-2020-03242 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 570 |
| 100 | 1 | _ | |a Hett, Erik C |0 P:(DE-HGF)0 |b 0 |e Corresponding author |
| 245 | _ | _ | |a Chemical genetics reveals a kinase-independent role for protein kinase R in pyroptosis. |
| 260 | _ | _ | |a Basingstoke |c 2013 |b Nature Publishing Group |
| 264 | _ | 1 | |3 online |2 Crossref |b Springer Science and Business Media LLC |c 2013-04-21 |
| 264 | _ | 1 | |3 print |2 Crossref |b Springer Science and Business Media LLC |c 2013-06-01 |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1585060229_943 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a 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. |
| 536 | _ | _ | |a 342 - Disease Mechanisms and Model Systems (POF3-342) |0 G:(DE-HGF)POF3-342 |c POF3-342 |f POF III |x 0 |
| 542 | _ | _ | |i 2013-04-21 |2 Crossref |u http://www.springer.com/tdm |
| 588 | _ | _ | |a Dataset connected to CrossRef, PubMed, |
| 650 | _ | 7 | |a HSP90 Heat-Shock Proteins |2 NLM Chemicals |
| 650 | _ | 7 | |a eIF-2 Kinase |0 EC 2.7.11.1 |2 NLM Chemicals |
| 650 | _ | 7 | |a Peptide Hydrolases |0 EC 3.4.- |2 NLM Chemicals |
| 650 | _ | 7 | |a Caspase 1 |0 EC 3.4.22.36 |2 NLM Chemicals |
| 650 | _ | 7 | |a Proteasome Endopeptidase Complex |0 EC 3.4.25.1 |2 NLM Chemicals |
| 650 | _ | 2 | |a Animals |2 MeSH |
| 650 | _ | 2 | |a Bacillus anthracis: enzymology |2 MeSH |
| 650 | _ | 2 | |a Caspase 1: metabolism |2 MeSH |
| 650 | _ | 2 | |a Catalytic Domain |2 MeSH |
| 650 | _ | 2 | |a Cell Death |2 MeSH |
| 650 | _ | 2 | |a Cell Line |2 MeSH |
| 650 | _ | 2 | |a Enzyme-Linked Immunosorbent Assay |2 MeSH |
| 650 | _ | 2 | |a HSP90 Heat-Shock Proteins: metabolism |2 MeSH |
| 650 | _ | 2 | |a Hydrogen-Ion Concentration |2 MeSH |
| 650 | _ | 2 | |a Inflammation |2 MeSH |
| 650 | _ | 2 | |a Macrophages: metabolism |2 MeSH |
| 650 | _ | 2 | |a Mice |2 MeSH |
| 650 | _ | 2 | |a Mice, Inbred BALB C |2 MeSH |
| 650 | _ | 2 | |a Models, Biological |2 MeSH |
| 650 | _ | 2 | |a Peptide Hydrolases: metabolism |2 MeSH |
| 650 | _ | 2 | |a Proteasome Endopeptidase Complex: metabolism |2 MeSH |
| 650 | _ | 2 | |a Protein Conformation |2 MeSH |
| 650 | _ | 2 | |a eIF-2 Kinase: chemistry |2 MeSH |
| 700 | 1 | _ | |a Slater, Louise H |0 P:(DE-HGF)0 |b 1 |
| 700 | 1 | _ | |a Mark, Kevin G |0 P:(DE-HGF)0 |b 2 |
| 700 | 1 | _ | |a Kawate, Tomohiko |0 P:(DE-HGF)0 |b 3 |
| 700 | 1 | _ | |a Monks, Brian G |0 P:(DE-HGF)0 |b 4 |
| 700 | 1 | _ | |a Stutz, Andrea |0 P:(DE-HGF)0 |b 5 |
| 700 | 1 | _ | |a Latz, Eicke |0 P:(DE-2719)2000062 |b 6 |u dzne |
| 700 | 1 | _ | |a Hung, Deborah T |0 P:(DE-HGF)0 |b 7 |
| 773 | 1 | 8 | |a 10.1038/nchembio.1236 |b : Springer Science and Business Media LLC, 2013-04-21 |n 6 |p 398-405 |3 journal-article |2 Crossref |t Nature Chemical Biology |v 9 |y 2013 |x 1552-4450 |
| 773 | _ | _ | |a 10.1038/nchembio.1236 |g Vol. 9, no. 6, p. 398 - 405 |0 PERI:(DE-600)2190276-8 |n 6 |q 9:6<398 - 405 |p 398-405 |t Nature chemical biology |v 9 |y 2013 |x 1552-4450 |
| 856 | 7 | _ | |2 Pubmed Central |u http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615456 |
| 909 | C | O | |o oai:pub.dzne.de:136920 |p VDB |
| 910 | 1 | _ | |a Deutsches Zentrum für Neurodegenerative Erkrankungen |0 I:(DE-588)1065079516 |k DZNE |b 6 |6 P:(DE-2719)2000062 |
| 913 | 1 | _ | |a DE-HGF |b Forschungsbereich Gesundheit |l Erkrankungen des Nervensystems |1 G:(DE-HGF)POF3-340 |0 G:(DE-HGF)POF3-342 |2 G:(DE-HGF)POF3-300 |v Disease Mechanisms and Model Systems |x 0 |
| 914 | 1 | _ | |y 2013 |
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| 915 | _ | _ | |a JCR |0 StatID:(DE-HGF)0100 |2 StatID |b NAT CHEM BIOL : 2017 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0200 |2 StatID |b SCOPUS |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0300 |2 StatID |b Medline |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0310 |2 StatID |b NCBI Molecular Biology Database |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0600 |2 StatID |b Ebsco Academic Search |
| 915 | _ | _ | |a Peer Review |0 StatID:(DE-HGF)0030 |2 StatID |b ASC |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0199 |2 StatID |b Clarivate Analytics Master Journal List |
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| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0150 |2 StatID |b Web of Science Core Collection |
| 915 | _ | _ | |a WoS |0 StatID:(DE-HGF)0111 |2 StatID |b Science Citation Index Expanded |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)1030 |2 StatID |b Current Contents - Life Sciences |
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