{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1361699995659276544.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1074/jbc.m209610200"}},{"identifier":{"@type":"URI","@value":"https://api.elsevier.com/content/article/PII:S0021925819324044?httpAccept=text/xml"}},{"identifier":{"@type":"URI","@value":"https://api.elsevier.com/content/article/PII:S0021925819324044?httpAccept=text/plain"}},{"identifier":{"@type":"URI","@value":"https://syndication.highwire.org/content/doi/10.1074/jbc.M209610200"}},{"identifier":{"@type":"PMID","@value":"12551927"}}],"dc:title":[{"@value":"Epoxycyclohexenone Inhibits Fas-mediated Apoptosis by Blocking Activation of Pro-caspase-8 in the Death-inducing Signaling Complex"}],"description":[{"notation":[{"@value":"Death receptors belong to the tumor necrosis factor receptor family. They can induce apoptosis following engagement with specific ligands and are known to play an important role in the regulation of the immune system. Here we report that epoxycyclohexenone (ECH) inhibits apoptosis induced by anti-Fas antibody, Fas ligand (FasL), or tumor necrosis factor-alpha but not by staurosporine, MG-132, C2-ceramide, or UV irradiation. These results suggest that ECH specifically blocks death receptor-mediated apoptosis. Neither the surface expression of Fas nor the Fas-FasL interaction was influenced by ECH. However, ECH did block the activation of pro-caspase-8 in the death-inducing signaling complex, although recruitment of Fas-associating death domain (FADD) and pro-caspase-8 was not affected. ECH inhibited the enzymatic activity of recombinant active caspase-8 at slightly lower concentrations than it did for active caspase-3 and active caspase-9 in vitro. However, in FasL-treated cells, ECH was only able to inhibit the activation of pro-caspase-8, and it had no effect on the already activated caspase-8 at a concentration that is effective at inhibiting Fas-induced apoptosis. ECH directly bound the large subunit of active caspase-8 that contains the active center cysteine and had a relatively higher affinity to pro-caspase-8. Moreover, compared with pro-caspase-3 and pro-caspase-9, pro-caspase-8 was predominantly depleted by biotinylated ECH with avidin beads in the cell lysates, suggesting that ECH preferentially affects pro-caspase-8. Thus, our results suggest that ECH blocks the self-activation of pro-caspase-8 in the death-inducing signaling complex and thus selectively inhibits death receptor-mediated apoptosis."}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1381699995659276544","@type":"Researcher","foaf:name":[{"@value":"Yasunobu Miyake"}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995659276545","@type":"Researcher","foaf:name":[{"@value":"Hideaki Kakeya"}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995659276672","@type":"Researcher","foaf:name":[{"@value":"Takao Kataoka"}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995659276673","@type":"Researcher","foaf:name":[{"@value":"Hiroyuki Osada"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00219258"}],"prism:publicationName":[{"@value":"Journal of Biological Chemistry"}],"dc:publisher":[{"@value":"Elsevier BV"}],"prism:publicationDate":"2003-03","prism:volume":"278","prism:number":"13","prism:startingPage":"11213","prism:endingPage":"11220"},"reviewed":"false","dcterms:accessRights":"http://purl.org/coar/access_right/c_abf2","dc:rights":["https://www.elsevier.com/tdm/userlicense/1.0/","http://creativecommons.org/licenses/by/4.0/"],"url":[{"@id":"https://api.elsevier.com/content/article/PII:S0021925819324044?httpAccept=text/xml"},{"@id":"https://api.elsevier.com/content/article/PII:S0021925819324044?httpAccept=text/plain"},{"@id":"https://syndication.highwire.org/content/doi/10.1074/jbc.M209610200"}],"createdAt":"2003-03-21","modifiedAt":"2024-01-09","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Caspase%208","dc:title":"Caspase 8"},{"@id":"https://cir.nii.ac.jp/all?q=Enzyme%20Precursors","dc:title":"Enzyme Precursors"},{"@id":"https://cir.nii.ac.jp/all?q=Base%20Sequence","dc:title":"Base Sequence"},{"@id":"https://cir.nii.ac.jp/all?q=Cyclohexanones","dc:title":"Cyclohexanones"},{"@id":"https://cir.nii.ac.jp/all?q=Apoptosis","dc:title":"Apoptosis"},{"@id":"https://cir.nii.ac.jp/all?q=Flow%20Cytometry","dc:title":"Flow Cytometry"},{"@id":"https://cir.nii.ac.jp/all?q=Caspase%209","dc:title":"Caspase 9"},{"@id":"https://cir.nii.ac.jp/all?q=Receptors,%20Tumor%20Necrosis%20Factor","dc:title":"Receptors, Tumor Necrosis Factor"},{"@id":"https://cir.nii.ac.jp/all?q=Enzyme%20Activation","dc:title":"Enzyme Activation"},{"@id":"https://cir.nii.ac.jp/all?q=Caspases","dc:title":"Caspases"},{"@id":"https://cir.nii.ac.jp/all?q=Tumor%20Cells,%20Cultured","dc:title":"Tumor Cells, Cultured"},{"@id":"https://cir.nii.ac.jp/all?q=Humans","dc:title":"Humans"},{"@id":"https://cir.nii.ac.jp/all?q=fas%20Receptor","dc:title":"fas Receptor"},{"@id":"https://cir.nii.ac.jp/all?q=DNA%20Primers","dc:title":"DNA Primers"}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360567183200940160","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Biosynthetic Origins of the Epoxyquinone Skeleton in Epoxyquinols A and B"}]},{"@id":"https://cir.nii.ac.jp/crid/1390282680289053696","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Novel Natural Products Open the Door of Chemical Biology and Medicinal Chemistry"},{"@language":"ja","@value":"新規有用天然有機化合物の開拓とケミカルバイオロジー研究"},{"@language":"ja-Kana","@value":"シンキ ユウヨウ テンネン ユウキ カゴウブツ ノ カイタク ト ケミカルバイオロジー ケンキュウ"},{"@value":"ChemInform Abstract: Novel Natural Products Open the Door of Chemical Biology and Medicinal Chemistry"}]},{"@id":"https://cir.nii.ac.jp/crid/1390282681453052416","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"RKTS-33, an Epoxycyclohexenone Derivative That Specifically Inhibits Fas Ligand-Dependent Apoptosis in CTL-Mediated Cytotoxicity"}]},{"@id":"https://cir.nii.ac.jp/crid/1390845713053783680","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"ja","@value":"Discovery Scienceに魅せられて"},{"@value":"Discovery Scienceに魅せられて : 天然物創薬ケミカルバイオロジーの最前線"},{"@language":"ja-Kana","@value":"Discovery Science ニ ミセラレテ : テンネンブツソウヤク ケミカルバイオロジー ノ サイゼンセン"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1074/jbc.m209610200"},{"@type":"OPENAIRE","@value":"doi_dedup___::8c497bddd72c20397e33ec347a57947b"},{"@type":"CROSSREF","@value":"10.1271/bbb.69.1923_references_DOI_Mks0o9OxBcwb0NxdgYplRKByaF7"},{"@type":"CROSSREF","@value":"10.1271/kagakutoseibutsu.56.210_references_DOI_Mks0o9OxBcwb0NxdgYplRKByaF7"},{"@type":"CROSSREF","@value":"10.5059/yukigoseikyokaishi.68.490_references_DOI_Mks0o9OxBcwb0NxdgYplRKByaF7"},{"@type":"CROSSREF","@value":"10.1021/np5004615_references_DOI_Mks0o9OxBcwb0NxdgYplRKByaF7"}]}