dc.contributor.author | Jaco, I | |
dc.contributor.author | Annibaldi, A | |
dc.contributor.author | Lalaoui, N | |
dc.contributor.author | Wilson, R | |
dc.contributor.author | Tenev, T | |
dc.contributor.author | Laurien, L | |
dc.contributor.author | Kim, C | |
dc.contributor.author | Jamal, K | |
dc.contributor.author | Wicky John, S | |
dc.contributor.author | Liccardi, G | |
dc.contributor.author | Chau, D | |
dc.contributor.author | Murphy, JM | |
dc.contributor.author | Brumatti, G | |
dc.contributor.author | Feltham, R | |
dc.contributor.author | Pasparakis, M | |
dc.contributor.author | Silke, J | |
dc.contributor.author | Meier, P | |
dc.date.accessioned | 2017-05-03T13:55:53Z | |
dc.date.issued | 2017-06-01 | |
dc.identifier.citation | Molecular cell, 2017, 66 (5), pp. 698 - 710.e5 | |
dc.identifier.issn | 1097-2765 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/628 | |
dc.identifier.eissn | 1097-4164 | |
dc.identifier.doi | 10.1016/j.molcel.2017.05.003 | |
dc.description.abstract | TNF is an inflammatory cytokine that upon binding to its receptor, TNFR1, can drive cytokine production, cell survival, or cell death. TNFR1 stimulation causes activation of NF-κB, p38α, and its downstream effector kinase MK2, thereby promoting transcription, mRNA stabilization, and translation of target genes. Here we show that TNF-induced activation of MK2 results in global RIPK1 phosphorylation. MK2 directly phosphorylates RIPK1 at residue S321, which inhibits its ability to bind FADD/caspase-8 and induce RIPK1-kinase-dependent apoptosis and necroptosis. Consistently, a phospho-mimetic S321D RIPK1 mutation limits TNF-induced death. Mechanistically, we find that phosphorylation of S321 inhibits RIPK1 kinase activation. We further show that cytosolic RIPK1 contributes to complex-II-mediated cell death, independent of its recruitment to complex-I, suggesting that complex-II originates from both RIPK1 in complex-I and cytosolic RIPK1. Thus, MK2-mediated phosphorylation of RIPK1 serves as a checkpoint within the TNF signaling pathway that integrates cell survival and cytokine production. | |
dc.format | Print-Electronic | |
dc.format.extent | 698 - 710.e5 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | CELL PRESS | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | HT29 Cells | |
dc.subject | Animals | |
dc.subject | Mice, Inbred C57BL | |
dc.subject | Mice, Knockout | |
dc.subject | Humans | |
dc.subject | Necrosis | |
dc.subject | Multiprotein Complexes | |
dc.subject | Protein-Serine-Threonine Kinases | |
dc.subject | MAP Kinase Kinase Kinases | |
dc.subject | Tumor Necrosis Factor-alpha | |
dc.subject | Intracellular Signaling Peptides and Proteins | |
dc.subject | Mitogen-Activated Protein Kinase 14 | |
dc.subject | NF-kappa B | |
dc.subject | Transfection | |
dc.subject | Signal Transduction | |
dc.subject | Apoptosis | |
dc.subject | RNA Interference | |
dc.subject | Phosphorylation | |
dc.subject | Dose-Response Relationship, Drug | |
dc.subject | Caspase 8 | |
dc.subject | Fas-Associated Death Domain Protein | |
dc.subject | Receptor-Interacting Protein Serine-Threonine Kinases | |
dc.title | MK2 Phosphorylates RIPK1 to Prevent TNF-Induced Cell Death. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2017-05-03 | |
rioxxterms.versionofrecord | 10.1016/j.molcel.2017.05.003 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2017-06 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Molecular cell | |
pubs.issue | 5 | |
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 | 66 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Cell Death and Immunity | |
dc.contributor.icrauthor | Jamal, Kunzah | |
dc.contributor.icrauthor | Meier, Pascal | |