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dc.contributor.authorHooftman, Alexander
dc.contributor.authorO'Neill, Luke
dc.date.accessioned2021-03-01T10:16:02Z
dc.date.available2021-03-01T10:16:02Z
dc.date.issued2019
dc.date.submitted2019en
dc.identifier.citationHughes, M.M., Hooftman, A., Angiari, S., Tummala, P., Zaslona, Z., Runtsch, M.C., McGettrick, A.F., Sutton, C.E., Diskin, C., Rooke, M., Takahashi, S., Sundararaj, S., Casarotto, M.G., Dahlstrom, J.E., Palsson-McDermott, E.M., Corr, S.C., Mills, K.H.G., Preston, R.J.S., Neamati, N., Xie, Y., Baell, J.B., Board, P.G., O'Neill, L.A.J., Glutathione Transferase Omega-1 Regulates NLRP3 Inflammasome Activation through NEK7 Deglutathionylation, Cell Reports, 2019, Oct 1;29(1):151-161.e5.en
dc.identifier.otherY
dc.identifier.urihttp://hdl.handle.net/2262/95418
dc.descriptionPUBLISHEDen
dc.description.abstractThe NLRP3 inflammasome is a cytosolic complex sensing phagocytosed material and various damage-associated molecular patterns, triggering production of the pro-inflammatory cytokines interleukin-1 beta (IL)-1β and IL-18 and promoting pyroptosis. Here, we characterize glutathione transferase omega 1-1 (GSTO1-1), a constitutive deglutathionylating enzyme, as a regulator of the NLRP3 inflammasome. Using a small molecule inhibitor of GSTO1-1 termed C1-27, endogenous GSTO1-1 knockdown, and GSTO1-1-/- mice, we report that GSTO1-1 is involved in NLRP3 inflammasome activation. Mechanistically, GSTO1-1 deglutathionylates cysteine 253 in NIMA related kinase 7 (NEK7) to promote NLRP3 activation. We therefore identify GSTO1-1 as an NLRP3 inflammasome regulator, which has potential as a drug target to limit NLRP3-mediated inflammation.en
dc.language.isoenen
dc.relation.ispartofseriesCell Reports;
dc.rightsYen
dc.subjectglutathione transferase omega 1-1 (GSTO1-1)en
dc.subjectNLRP3 activationen
dc.subjectpro-inflammatory cytokines interleukin-1 beta (IL)-1βen
dc.subjectGSTO1-1en
dc.subjectIL-1βen
dc.subjectNEK7en
dc.subjectNLRP3 inflammasomeen
dc.subjectDeglutathionylationen
dc.subjectGlutathioneen
dc.subjectPyroptosisen
dc.titleGlutathione Transferase Omega-1 Regulates NLRP3 Inflammasome Activation through NEK7 Deglutathionylationen
dc.typeJournal Articleen
dc.contributor.sponsorScience Foundation Irelanden
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/laoneill
dc.identifier.peoplefinderurlhttp://people.tcd.ie/ahooftma
dc.identifier.rssinternalid222189
dc.identifier.doihttps://doi-org.elib.tcd.ie/10.1016/j.celrep.2019.08.072
dc.rights.ecaccessrightsopenAccess
dc.contributor.sponsorGrantNumberSFI 12/IA/1531en


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