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dc.contributor.authorJaco, I
dc.contributor.authorAnnibaldi, A
dc.contributor.authorLalaoui, N
dc.contributor.authorWilson, R
dc.contributor.authorTenev, T
dc.contributor.authorLaurien, L
dc.contributor.authorKim, C
dc.contributor.authorJamal, K
dc.contributor.authorJohn, SW
dc.contributor.authorLiccardi, G
dc.contributor.authorChau, D
dc.contributor.authorMurphy, JM
dc.contributor.authorBrumatti, G
dc.contributor.authorFeltham, R
dc.contributor.authorPasparakis, M
dc.contributor.authorSilke, J
dc.contributor.authorMeier, P
dc.date.accessioned2021-02-04T01:08:03Z
dc.date.available2021-02-04T01:08:03Z
dc.date.issued2017-06-01
dc.identifierpii: S1097-2765(17)30316-7
dc.identifier.citationJaco, I., Annibaldi, A., Lalaoui, N., Wilson, R., Tenev, T., Laurien, L., Kim, C., Jamal, K., John, S. W., Liccardi, G., Chau, D., Murphy, J. M., Brumatti, G., Feltham, R., Pasparakis, M., Silke, J. & Meier, P. (2017). MK2 Phosphorylates RIPK1 to Prevent TNF-Induced Cell Death. MOLECULAR CELL, 66 (5), pp.698-+. https://doi.org/10.1016/j.molcel.2017.05.003.
dc.identifier.issn1097-2765
dc.identifier.urihttp://hdl.handle.net/11343/259271
dc.description.abstractTNF 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.languageEnglish
dc.publisherCELL PRESS
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleMK2 Phosphorylates RIPK1 to Prevent TNF-Induced Cell Death
dc.typeJournal Article
dc.identifier.doi10.1016/j.molcel.2017.05.003
melbourne.affiliation.departmentMedical Biology (W.E.H.I.)
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titleMolecular Cell
melbourne.source.volume66
melbourne.source.issue5
melbourne.source.pages698-+
dc.rights.licenseCC BY
melbourne.elementsid1210015
melbourne.contributor.authorLalaoui, Najoua
melbourne.contributor.authorMurphy, James
melbourne.contributor.authorBrumatti, Gabriela
melbourne.contributor.authorFeltham, Rebecca
melbourne.contributor.authorSilke, John
dc.identifier.eissn1097-4164
melbourne.accessrightsOpen Access


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