412 550

Cited 788 times in

The pyroptosome: a supramolecular assembly of ASC dimers mediating inflammatory cell death via caspase-1 activation

DC Field Value Language
dc.contributor.author유제욱-
dc.date.accessioned2014-12-21T16:30:08Z-
dc.date.available2014-12-21T16:30:08Z-
dc.date.issued2007-
dc.identifier.issn1350-9047-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/95812-
dc.description.abstractPyroptosis is a caspase-1-dependent inflammatory form of cell death. The adapter protein ASC binds directly to caspase-1 and is critical for caspase-1 activation in response to a broad range of stimuli. To elucidate the mechanism of activation of caspase-1 by ASC and its exact role in macrophage pyroptosis, we performed time-lapse confocal bioimaging analysis on human THP-1 macrophages stably expressing an ASC–GFP fusion protein. We show that stimulation of these cells with several proinflammatory stimuli trigger the formation of a large supramolecular assembly of ASC, termed here pyroptosome. Only one distinct pyroptosome in each stimulated cell is formed, which rapidly recruits and activates caspase-1 resulting in pyroptosis and the release of the intracellular proinflammatory cytokines. The pyroptosome is largely composed of oligomerized ASC dimers. Dimerization of ASC is driven by subphysiological concentrations of potassium as in vitro incubation of purified recombinant ASC in the presence of subphysiological concentrations of potassium induces the assembly of a functional pyroptosome. Furthermore, stimulation of potassium efflux in THP-1 cells with potassium-depleting agents induces formation of the pyroptosome, while increasing potassium concentrations in the culture medium or pharmacological inhibition of this efflux inhibits its assembly. Our results establish that macrophage pyroptosis is mediated by a unique pyroptosome, distinct from the inflammasome.-
dc.description.statementOfResponsibilityopen-
dc.format.extent1590~1604-
dc.relation.isPartOfCELL DEATH AND DIFFERENTIATION-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.titleThe pyroptosome: a supramolecular assembly of ASC dimers mediating inflammatory cell death via caspase-1 activation-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Microbiology (미생물학)-
dc.contributor.googleauthorT Fernandes-Alnemri-
dc.contributor.googleauthorJ Wu-
dc.contributor.googleauthorE S Alnemri-
dc.contributor.googleauthorJ Zhang-
dc.contributor.googleauthorS Rosenberg-
dc.contributor.googleauthorW Jankowski-
dc.contributor.googleauthorB Miller-
dc.contributor.googleauthorP Datta-
dc.contributor.googleauthorJ-W Yu-
dc.identifier.doi10.1038/sj.cdd.4402194-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA02508-
dc.relation.journalcodeJ00483-
dc.identifier.eissn1476-5403-
dc.contributor.alternativeNameYu, Je Wook-
dc.contributor.affiliatedAuthorYu, Je Wook-
dc.rights.accessRightsfree-
dc.citation.volume14-
dc.citation.number9-
dc.citation.startPage1590-
dc.citation.endPage1604-
dc.identifier.bibliographicCitationCELL DEATH AND DIFFERENTIATION, Vol.14(9) : 1590-1604, 2007-
dc.identifier.rimsid53222-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.