dc.contributor.author | Annibaldi, A | |
dc.contributor.author | Wicky John, S | |
dc.contributor.author | Vanden Berghe, T | |
dc.contributor.author | Swatek, KN | |
dc.contributor.author | Ruan, J | |
dc.contributor.author | Liccardi, G | |
dc.contributor.author | Bianchi, K | |
dc.contributor.author | Elliott, PR | |
dc.contributor.author | Choi, SM | |
dc.contributor.author | Van Coillie, S | |
dc.contributor.author | Bertin, J | |
dc.contributor.author | Wu, H | |
dc.contributor.author | Komander, D | |
dc.contributor.author | Vandenabeele, P | |
dc.contributor.author | Silke, J | |
dc.contributor.author | Meier, P | |
dc.date.accessioned | 2018-01-24T11:49:05Z | |
dc.date.issued | 2018-02-15 | |
dc.identifier.citation | Molecular cell, 2018, 69 (4), pp. 566 - 580.e5 | |
dc.identifier.issn | 1097-2765 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/1012 | |
dc.identifier.eissn | 1097-4164 | |
dc.identifier.doi | 10.1016/j.molcel.2018.01.027 | |
dc.description.abstract | Tumor necrosis factor (TNF) can drive inflammation, cell survival, and death. While ubiquitylation-, phosphorylation-, and nuclear factor κB (NF-κB)-dependent checkpoints suppress the cytotoxic potential of TNF, it remains unclear whether ubiquitylation can directly repress TNF-induced death. Here, we show that ubiquitylation regulates RIPK1's cytotoxic potential not only via activation of downstream kinases and NF-kB transcriptional responses, but also by directly repressing RIPK1 kinase activity via ubiquitin-dependent inactivation. We find that the ubiquitin-associated (UBA) domain of cellular inhibitor of apoptosis (cIAP)1 is required for optimal ubiquitin-lysine occupancy and K48 ubiquitylation of RIPK1. Independently of IKK and MK2, cIAP1-mediated and UBA-assisted ubiquitylation suppresses RIPK1 kinase auto-activation and, in addition, marks it for proteasomal degradation. In the absence of a functional UBA domain of cIAP1, more active RIPK1 kinase accumulates in response to TNF, causing RIPK1 kinase-mediated cell death and systemic inflammatory response syndrome. These results reveal a direct role for cIAP-mediated ubiquitylation in controlling RIPK1 kinase activity and preventing TNF-mediated cytotoxicity. | |
dc.format | Print | |
dc.format.extent | 566 - 580.e5 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | CELL PRESS | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Animals | |
dc.subject | Mice, Inbred C57BL | |
dc.subject | Mice, Knockout | |
dc.subject | Humans | |
dc.subject | Mice | |
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 | NF-kappa B | |
dc.subject | Ubiquitin | |
dc.subject | Signal Transduction | |
dc.subject | Apoptosis | |
dc.subject | Inhibitor of Apoptosis Proteins | |
dc.subject | I-kappa B Kinase | |
dc.subject | Receptor-Interacting Protein Serine-Threonine Kinases | |
dc.subject | Ubiquitination | |
dc.subject | HEK293 Cells | |
dc.subject | Baculoviral IAP Repeat-Containing 3 Protein | |
dc.title | Ubiquitin-Mediated Regulation of RIPK1 Kinase Activity Independent of IKK and MK2. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2018-01-19 | |
rioxxterms.versionofrecord | 10.1016/j.molcel.2018.01.027 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2018-02 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Molecular cell | |
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 | 69 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Cell Death and Immunity | |
dc.contributor.icrauthor | Wicky John, Sidonie | |
dc.contributor.icrauthor | Meier, Pascal | |