University Library
  • Login
A gateway to Melbourne's research publications
Minerva Access is the University's Institutional Repository. It aims to collect, preserve, and showcase the intellectual output of staff and students of the University of Melbourne for a global audience.
View Item 
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Medical Biology
  • Medical Biology - Research Publications
  • View Item
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Medical Biology
  • Medical Biology - Research Publications
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

    MK2 Phosphorylates RIPK1 to Prevent TNF-Induced Cell Death

    Thumbnail
    Download
    Published version (3.597Mb)

    Citations
    Scopus
    Altmetric
    109
    Author
    Jaco, I; Annibaldi, A; Lalaoui, N; Wilson, R; Tenev, T; Laurien, L; Kim, C; Jamal, K; John, SW; Liccardi, G; ...
    Date
    2017-06-01
    Source Title
    Molecular Cell
    Publisher
    CELL PRESS
    University of Melbourne Author/s
    Lalaoui, Najoua; Murphy, James; Brumatti, Gabriela; Feltham, Rebecca; Silke, John
    Affiliation
    Medical Biology (W.E.H.I.)
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Jaco, 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.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/259271
    DOI
    10.1016/j.molcel.2017.05.003
    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.

    Export Reference in RIS Format     

    Endnote

    • Click on "Export Reference in RIS Format" and choose "open with... Endnote".

    Refworks

    • Click on "Export Reference in RIS Format". Login to Refworks, go to References => Import References


    Collections
    • Minerva Elements Records [52369]
    • Medical Biology - Research Publications [1412]
    Minerva AccessDepositing Your Work (for University of Melbourne Staff and Students)NewsFAQs

    BrowseCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects
    My AccountLoginRegister
    StatisticsMost Popular ItemsStatistics by CountryMost Popular Authors