Show simple item record

dc.contributor.authorFeltham, R
dc.contributor.authorJamal, K
dc.contributor.authorTenev, T
dc.contributor.authorLiccardi, G
dc.contributor.authorJaco, I
dc.contributor.authorDomingues, CM
dc.contributor.authorMorris, O
dc.contributor.authorJohn, SW
dc.contributor.authorAnnibaldi, A
dc.contributor.authorWidya, M
dc.contributor.authorKearney, CJ
dc.contributor.authorClancy, D
dc.contributor.authorElliott, PR
dc.contributor.authorGlatter, T
dc.contributor.authorQiao, Q
dc.contributor.authorThompson, AJ
dc.contributor.authorNesvizhskii, A
dc.contributor.authorSchmidt, A
dc.contributor.authorKomander, D
dc.contributor.authorWu, H
dc.contributor.authorMartin, S
dc.contributor.authorMeier, P
dc.date.accessioned2018-03-16T10:26:47Z
dc.date.issued2018-04-10
dc.identifier.citationCell reports, 2018, 23 (2), pp. 470 - 484
dc.identifier.issn2211-1247
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1598
dc.identifier.eissn2211-1247
dc.identifier.doi10.1016/j.celrep.2018.03.054
dc.description.abstractTumor 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.formatPrint
dc.format.extent470 - 484
dc.languageeng
dc.language.isoeng
dc.publisherCELL PRESS
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectCell Line, Tumor
dc.subjectHumans
dc.subjectUbiquitin-Protein Ligases
dc.subjectLipopolysaccharides
dc.subjectTumor Necrosis Factor-alpha
dc.subjectNF-kappa B
dc.subjectRNA, Small Interfering
dc.subjectSignal Transduction
dc.subjectApoptosis
dc.subjectRNA Interference
dc.subjectToll-Like Receptor 4
dc.subjectCaspase 8
dc.subjectReceptor-Interacting Protein Serine-Threonine Kinases
dc.subjectUbiquitination
dc.subjectProtein Multimerization
dc.subjectHEK293 Cells
dc.titleMind Bomb Regulates Cell Death during TNF Signaling by Suppressing RIPK1's Cytotoxic Potential.
dc.typeJournal Article
dcterms.dateAccepted2018-03-13
rioxxterms.versionofrecord10.1016/j.celrep.2018.03.054
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2018-04
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCell reports
pubs.issue2
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/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-statusPublished
pubs.volume23
pubs.embargo.termsNot known
icr.researchteamCell Death and Immunity
icr.researchteamTarget Discovery & Apoptosis
dc.contributor.icrauthorJamal, Kunzah
dc.contributor.icrauthorMorris, Otto
dc.contributor.icrauthorMeier, Pascal


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