dc.contributor.author | Martinez Lagunas, K | |
dc.contributor.author | Savcigil, DP | |
dc.contributor.author | Zrilic, M | |
dc.contributor.author | Carvajal Fraile, C | |
dc.contributor.author | Craxton, A | |
dc.contributor.author | Self, E | |
dc.contributor.author | Uranga-Murillo, I | |
dc.contributor.author | de Miguel, D | |
dc.contributor.author | Arias, M | |
dc.contributor.author | Willenborg, S | |
dc.contributor.author | Piekarek, M | |
dc.contributor.author | Albert, MC | |
dc.contributor.author | Nugraha, K | |
dc.contributor.author | Lisewski, I | |
dc.contributor.author | Janakova, E | |
dc.contributor.author | Igual, N | |
dc.contributor.author | Tonnus, W | |
dc.contributor.author | Hildebrandt, X | |
dc.contributor.author | Ibrahim, M | |
dc.contributor.author | Ballegeer, M | |
dc.contributor.author | Saelens, X | |
dc.contributor.author | Kueh, A | |
dc.contributor.author | Meier, P | |
dc.contributor.author | Linkermann, A | |
dc.contributor.author | Pardo, J | |
dc.contributor.author | Eming, S | |
dc.contributor.author | Walczak, H | |
dc.contributor.author | MacFarlane, M | |
dc.contributor.author | Peltzer, N | |
dc.contributor.author | Annibaldi, A | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2023-10-20T13:23:52Z | |
dc.date.available | 2023-10-20T13:23:52Z | |
dc.date.issued | 2023-07-28 | |
dc.identifier | ARTN eadg2829 | |
dc.identifier.citation | Science Advances, 2023, 9 (30), pp. eadg2829 - | |
dc.identifier.issn | 2375-2548 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/6026 | |
dc.identifier.eissn | 2375-2548 | |
dc.identifier.eissn | 2375-2548 | |
dc.identifier.doi | 10.1126/sciadv.adg2829 | |
dc.identifier.doi | 10.1126/sciadv.adg2829 | |
dc.description.abstract | Cell death coordinates repair programs following pathogen attack and tissue injury. However, aberrant cell death can interfere with such programs and cause organ failure. Cellular FLICE-like inhibitory protein (cFLIP) is a crucial regulator of cell death and a substrate of Caspase-8. However, the physiological role of cFLIP cleavage by Caspase-8 remains elusive. Here, we found an essential role for cFLIP cleavage in restraining cell death in different pathophysiological scenarios. Mice expressing a cleavage-resistant cFLIP mutant, CflipD377A, exhibited increased sensitivity to severe acute respiratory syndrome coronavirus (SARS-CoV)-induced lethality, impaired skin wound healing, and increased tissue damage caused by Sharpin deficiency. In vitro, abrogation of cFLIP cleavage sensitizes cells to tumor necrosis factor(TNF)-induced necroptosis and apoptosis by favoring complex-II formation. Mechanistically, the cell death-sensitizing effect of the D377A mutation depends on glutamine-469. These results reveal a crucial role for cFLIP cleavage in controlling the amplitude of cell death responses occurring upon tissue stress to ensure the execution of repair programs. | |
dc.format | Print-Electronic | |
dc.format.extent | eadg2829 - | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | AMER ASSOC ADVANCEMENT SCIENCE | |
dc.relation.ispartof | Science Advances | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | Animals | |
dc.subject | Mice | |
dc.subject | Caspase 8 | |
dc.subject | Apoptosis | |
dc.subject | Skin | |
dc.subject | Tumor Necrosis Factor-alpha | |
dc.subject | Virus Diseases | |
dc.title | Cleavage of cFLIP restrains cell death during viral infection and tissue injury and favors tissue repair. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2023-06-22 | |
dc.date.updated | 2023-10-20T13:22:46Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1126/sciadv.adg2829 | |
rioxxterms.licenseref.startdate | 2023-07-28 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/37494451 | |
pubs.issue | 30 | |
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.publisher-url | http://dx.doi.org/10.1126/sciadv.adg2829 | |
pubs.volume | 9 | |
icr.researchteam | Cell Death and Immunity | |
dc.contributor.icrauthor | Meier, Pascal | |
icr.provenance | Deposited by Mr Arek Surman on 2023-10-20. Deposit type is initial. No. of files: 1. Files: Cleavage of cFLIP restrains cell death during viral infection and tissue injury and favors tissue repair.pdf | |