dc.contributor.author | Feltham, R | |
dc.contributor.author | Jamal, K | |
dc.contributor.author | Tenev, T | |
dc.contributor.author | Liccardi, G | |
dc.contributor.author | Jaco, I | |
dc.contributor.author | Domingues, CM | |
dc.contributor.author | Morris, O | |
dc.contributor.author | John, SW | |
dc.contributor.author | Annibaldi, A | |
dc.contributor.author | Widya, M | |
dc.contributor.author | Kearney, CJ | |
dc.contributor.author | Clancy, D | |
dc.contributor.author | Elliott, PR | |
dc.contributor.author | Glatter, T | |
dc.contributor.author | Qiao, Q | |
dc.contributor.author | Thompson, AJ | |
dc.contributor.author | Nesvizhskii, A | |
dc.contributor.author | Schmidt, A | |
dc.contributor.author | Komander, D | |
dc.contributor.author | Wu, H | |
dc.contributor.author | Martin, S | |
dc.contributor.author | Meier, P | |
dc.date.accessioned | 2018-03-16T10:26:47Z | |
dc.date.issued | 2018-04-10 | |
dc.identifier.citation | Cell reports, 2018, 23 (2), pp. 470 - 484 | |
dc.identifier.issn | 2211-1247 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/1598 | |
dc.identifier.eissn | 2211-1247 | |
dc.identifier.doi | 10.1016/j.celrep.2018.03.054 | |
dc.description.abstract | Tumor necrosis factor (TNF) is an inflammatory cytokine that can signal cell survival or cell death. The mechanisms that switch between these distinct outcomes remain poorly defined. Here, we show that the E3 ubiquitin ligase Mind Bomb-2 (MIB2) regulates TNF-induced cell death by inactivating RIPK1 via inhibitory ubiquitylation. Although depletion of MIB2 has little effect on NF-κB activation, it sensitizes cells to RIPK1- and caspase-8-dependent cell death. We find that MIB2 represses the cytotoxic potential of RIPK1 by ubiquitylating lysine residues in the C-terminal portion of RIPK1. Our data suggest that ubiquitin conjugation of RIPK1 interferes with RIPK1 oligomerization and RIPK1-FADD association. Disruption of MIB2-mediated ubiquitylation, either by mutation of MIB2's E3 activity or RIPK1's ubiquitin-acceptor lysines, sensitizes cells to RIPK1-mediated cell death. Together, our findings demonstrate that Mind Bomb E3 ubiquitin ligases can function as additional checkpoint of cytokine-induced cell death, selectively protecting cells from the cytotoxic effects of TNF. | |
dc.format | Print | |
dc.format.extent | 470 - 484 | |
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, Tumor | |
dc.subject | Humans | |
dc.subject | Ubiquitin-Protein Ligases | |
dc.subject | Lipopolysaccharides | |
dc.subject | Tumor Necrosis Factor-alpha | |
dc.subject | NF-kappa B | |
dc.subject | RNA, Small Interfering | |
dc.subject | Signal Transduction | |
dc.subject | Apoptosis | |
dc.subject | RNA Interference | |
dc.subject | Toll-Like Receptor 4 | |
dc.subject | Caspase 8 | |
dc.subject | Receptor-Interacting Protein Serine-Threonine Kinases | |
dc.subject | Ubiquitination | |
dc.subject | Protein Multimerization | |
dc.subject | HEK293 Cells | |
dc.title | Mind Bomb Regulates Cell Death during TNF Signaling by Suppressing RIPK1's Cytotoxic Potential. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2018-03-13 | |
rioxxterms.versionofrecord | 10.1016/j.celrep.2018.03.054 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2018-04 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Cell reports | |
pubs.issue | 2 | |
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/Primary Group/ICR Divisions/Breast Cancer Research/Target Discovery & Apoptosis | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Target Discovery & Apoptosis | |
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/Primary Group/ICR Divisions/Breast Cancer Research/Target Discovery & Apoptosis | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Target Discovery & Apoptosis | |
pubs.publication-status | Published | |
pubs.volume | 23 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Cell Death and Immunity | |
icr.researchteam | Target Discovery & Apoptosis | |
dc.contributor.icrauthor | Jamal, Kunzah | |
dc.contributor.icrauthor | Morris, Otto | |
dc.contributor.icrauthor | Meier, Pascal | |