dc.contributor.author | Horn, S | |
dc.contributor.author | Hughes, MA | |
dc.contributor.author | Schilling, R | |
dc.contributor.author | Sticht, C | |
dc.contributor.author | Tenev, T | |
dc.contributor.author | Ploesser, M | |
dc.contributor.author | Meier, P | |
dc.contributor.author | Sprick, MR | |
dc.contributor.author | MacFarlane, M | |
dc.contributor.author | Leverkus, M | |
dc.date.accessioned | 2017-05-23T14:53:36Z | |
dc.date.issued | 2017-04-25 | |
dc.identifier.citation | Cell reports, 2017, 19 (4), pp. 785 - 797 | |
dc.identifier.issn | 2211-1247 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/643 | |
dc.identifier.eissn | 2211-1247 | |
dc.identifier.doi | 10.1016/j.celrep.2017.04.010 | |
dc.description.abstract | Formation 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.format | Print | |
dc.format.extent | 785 - 797 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | CELL PRESS | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Cell Line | |
dc.subject | Hela Cells | |
dc.subject | Humans | |
dc.subject | Imidazoles | |
dc.subject | Indoles | |
dc.subject | Oligopeptides | |
dc.subject | NF-kappa B | |
dc.subject | RNA, Small Interfering | |
dc.subject | RNA, Messenger | |
dc.subject | Interleukin-8 | |
dc.subject | Signal Transduction | |
dc.subject | Apoptosis | |
dc.subject | Cell Survival | |
dc.subject | RNA Interference | |
dc.subject | Caspase 8 | |
dc.subject | CASP8 and FADD-Like Apoptosis Regulating Protein | |
dc.subject | Fas Ligand Protein | |
dc.subject | Fas-Associated Death Domain Protein | |
dc.subject | Caspase 10 | |
dc.subject | Clustered Regularly Interspaced Short Palindromic Repeats | |
dc.subject | NF-KappaB Inhibitor alpha | |
dc.subject | fas Receptor | |
dc.title | Caspase-10 Negatively Regulates Caspase-8-Mediated Cell Death, Switching the Response to CD95L in Favor of NF-κB Activation and Cell Survival. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2017-04-03 | |
rioxxterms.versionofrecord | 10.1016/j.celrep.2017.04.010 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2017-04 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Cell reports | |
pubs.issue | 4 | |
pubs.notes | Not 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-status | Published | |
pubs.volume | 19 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Cell Death and Immunity | |
dc.contributor.icrauthor | Meier, Pascal | |