Show simple item record

dc.contributor.authorHorn, S
dc.contributor.authorHughes, MA
dc.contributor.authorSchilling, R
dc.contributor.authorSticht, C
dc.contributor.authorTenev, T
dc.contributor.authorPloesser, M
dc.contributor.authorMeier, P
dc.contributor.authorSprick, MR
dc.contributor.authorMacFarlane, M
dc.contributor.authorLeverkus, M
dc.date.accessioned2017-05-23T14:53:36Z
dc.date.issued2017-04
dc.identifier.citationCell reports, 2017, 19 (4), pp. 785 - 797
dc.identifier.issn2211-1247
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/643
dc.identifier.eissn2211-1247
dc.identifier.doi10.1016/j.celrep.2017.04.010
dc.description.abstractFormation of the death-inducing signaling complex (DISC) initiates extrinsic apoptosis. Caspase-8 and its regulator cFLIP control death signaling by binding to death-receptor-bound FADD. By elucidating the function of the caspase-8 homolog, caspase-10, we discover that caspase-10 negatively regulates caspase-8-mediated cell death. Significantly, we reveal that caspase-10 reduces DISC association and activation of caspase-8. Furthermore, we extend our co-operative/hierarchical binding model of caspase-8/cFLIP and show that caspase-10 does not compete with caspase-8 for binding to FADD. Utilizing caspase-8-knockout cells, we demonstrate that caspase-8 is required upstream of both cFLIP and caspase-10 and that DISC formation critically depends on the scaffold function of caspase-8. We establish that caspase-10 rewires DISC signaling to NF-κB activation/cell survival and demonstrate that the catalytic activity of caspase-10, and caspase-8, is redundant in gene induction. Thus, our data are consistent with a model in which both caspase-10 and cFLIP coordinately regulate CD95L-mediated signaling for death or survival.
dc.formatPrint
dc.format.extent785 - 797
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectCell Line
dc.subjectHela Cells
dc.subjectHumans
dc.subjectImidazoles
dc.subjectIndoles
dc.subjectOligopeptides
dc.subjectNF-kappa B
dc.subjectRNA, Small Interfering
dc.subjectRNA, Messenger
dc.subjectInterleukin-8
dc.subjectSignal Transduction
dc.subjectApoptosis
dc.subjectCell Survival
dc.subjectRNA Interference
dc.subjectCaspase 8
dc.subjectCASP8 and FADD-Like Apoptosis Regulating Protein
dc.subjectFas Ligand Protein
dc.subjectFas-Associated Death Domain Protein
dc.subjectCaspase 10
dc.subjectClustered Regularly Interspaced Short Palindromic Repeats
dc.subjectNF-KappaB Inhibitor alpha
dc.subjectfas Receptor
dc.titleCaspase-10 Negatively Regulates Caspase-8-Mediated Cell Death, Switching the Response to CD95L in Favor of NF-κB Activation and Cell Survival.
dc.typeJournal Article
dcterms.dateAccepted2017-04-03
rioxxterms.versionofrecord10.1016/j.celrep.2017.04.010
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2017-04
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCell reports
pubs.issue4
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Cell Death and Immunity
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Cell Death and Immunity
pubs.publication-statusPublished
pubs.volume19
pubs.embargo.termsNot known
icr.researchteamCell Death and Immunityen_US
dc.contributor.icrauthorMeier, Pascalen


Files in this item

Thumbnail

This item appears in the following collection(s)

Show simple item record

https://creativecommons.org/licenses/by/4.0
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0