Role of FLASH in caspase-8-mediated activation of NF-κB: dominant-negative function of FLASH mutant in NF-κB signaling pathway

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dc.contributor.authorJ I Jun-
dc.contributor.authorC W Chung-
dc.contributor.authorH J Lee-
dc.contributor.authorJ O Pyo-
dc.contributor.authorKee Nyung Lee-
dc.contributor.authorNam-Soon Kim-
dc.contributor.authorYong Sung Kim-
dc.contributor.authorHyang Sook Yoo-
dc.contributor.authorT H Lee-
dc.contributor.authorE Kim-
dc.contributor.authorY K Jung-
dc.date.accessioned2017-04-19T09:02:18Z-
dc.date.available2017-04-19T09:02:18Z-
dc.date.issued2005-
dc.identifier.issn0950-9232-
dc.identifier.uri10.1038/sj.onc.1208186ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/6822-
dc.description.abstractCaspase-8 is the most receptor-proximal, upstream caspase in the caspase cascade and plays a key role in cell death triggered by various death receptors. Here, we addressed the role of endogenous caspase-8 in tumor necrosis factor (TNF)-α-induced activation of NF-κB. Direct targeting of caspase-8 with siRNA and antisense (AS) approaches abolished TNF-α-induced activation of NF-κB in NIH3T3, HeLa, and HEK293 cells as determined with luciferase reporter gene and cell fractionation assays. Reconstitution of caspase-8-deficient C33A cells with processing-defective (P/D) mutant of caspase-8 sensitized the cells to TNF-α for NF-κB activation. In contrast to wild-type caspase-8, death effector domain mutant replacing Asp73 with Ala (caspase-8 (D73A)) failed to activate NF-κB and to bind FLICE-associated huge protein (FLASH) in vitro and in vivo. Instead, caspase-8 (D73A) mutant bound to caspase-8 and blocked NF-κB activation triggered by TNF-α and caspase-8. In addition, expression of an NF-κB-activating domain-deletion mutant of FLASH or transfection of FLASH AS oligonucleotides abolished TNF-α and caspase-8, but not phorbol 12-myristate 13-acetate, -induced activation of NF-κB. Further, immunoprecipitation assays showed that caspase-8 formed triple complex with TRAF2 and FLASH. Taken together, these results suggest that endogenous caspase-8 mediates TNF-α-induced activation of NF-κB via FLASH.-
dc.publisherSpringer-Nature Pub Group-
dc.titleRole of FLASH in caspase-8-mediated activation of NF-κB: dominant-negative function of FLASH mutant in NF-κB signaling pathway-
dc.title.alternativeRole of FLASH in caspase-8-mediated activation of NF-κB: dominant-negative function of FLASH mutant in NF-κB signaling pathway-
dc.typeArticle-
dc.citation.titleOncogene-
dc.citation.number4-
dc.citation.endPage696-
dc.citation.startPage688-
dc.citation.volume24-
dc.contributor.affiliatedAuthorKee Nyung Lee-
dc.contributor.affiliatedAuthorNam-Soon Kim-
dc.contributor.affiliatedAuthorYong Sung Kim-
dc.contributor.affiliatedAuthorHyang Sook Yoo-
dc.contributor.alternativeName전준일-
dc.contributor.alternativeName정철웅-
dc.contributor.alternativeName이호준-
dc.contributor.alternativeName표종옥-
dc.contributor.alternativeName이기녕-
dc.contributor.alternativeName김남순-
dc.contributor.alternativeName김용성-
dc.contributor.alternativeName유향숙-
dc.contributor.alternativeName이태호-
dc.contributor.alternativeName김은희-
dc.contributor.alternativeName정용근-
dc.identifier.bibliographicCitationOncogene, vol. 24, no. 4, pp. 688-696-
dc.identifier.doi10.1038/sj.onc.1208186-
dc.subject.keywordCaspase-8-
dc.subject.keywordDominant negative-
dc.subject.keywordFLASH-
dc.subject.keywordNF-κB-
dc.subject.keywordSiRNA-
dc.subject.localCaspase-8-
dc.subject.localDominant negative-
dc.subject.localFLASH-
dc.subject.localNuclear factor-kappa B-
dc.subject.localnuclear factor κB-
dc.subject.localNf-κb-
dc.subject.localNF-kB-
dc.subject.localnuclear factor kappa B-
dc.subject.localNF-κB (nuclear factor kappa-B)-
dc.subject.localNF-kappaB-
dc.subject.localNuclear factor-κb-
dc.subject.localNF-κ B-
dc.subject.localNF-κB-
dc.subject.localNF-kappa B-
dc.subject.localNuclear factor κB (NF-κB)-
dc.subject.localNuclear factor κB-
dc.subject.localNFκB-
dc.subject.localNf-κB-
dc.subject.localNuclear factor-κB-
dc.subject.localnuclear factorκB-
dc.subject.localNuclear factor (NF)-κB-
dc.subject.localNuclear factor kappa B-
dc.subject.localnuclear factor-κB-
dc.subject.localNF-ΚB-
dc.subject.localNuclear factor-kappa B (NF-κB)-
dc.subject.localNuclear factor-kappaB-
dc.subject.localnuclear factor-kappaB-
dc.subject.localnuclear factor-kappaB (NF-κB)-
dc.subject.localNFkappaB-
dc.subject.localNuclear factor kappaB-
dc.subject.localsiRNA-
dc.subject.localSiRNA-
dc.description.journalClassY-
Appears in Collections:
Division of Biomedical Research > Rare Disease Research Center > 1. Journal Articles
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