Ubiquitylation of the initiator caspase DREDD is required for innate immune signalling

Annika Meinander, C Runchel, T Tenev, L Chen, CH Kim, PS Ribeiro, M Broemer, F Leulier, M Zvelebil, N Silverman, P Meier

    Research output: Contribution to journalArticleScientificpeer-review

    56 Citations (Scopus)

    Abstract

    Caspases have been extensively studied as critical initiators and executioners of cell death pathways. However, caspases also take part in non-apoptotic signalling events such as the regulation of innate immunity and activation of nuclear factor-kappa B (NF-kappa B). How caspases are activated under these conditions and process a selective set of substrates to allow NF-kappa B signalling without killing the cell remains largely unknown. Here, we show that stimulation of the Drosophila pattern recognition protein PGRP-LCx induces DIAP2-dependent polyubiquitylation of the initiator caspase DREDD. Signal-dependent ubiquitylation of DREDD is required for full processing of IMD, NF-kappa B/Relish and expression of antimicrobial peptide genes in response to infection with Gram-negative bacteria. Our results identify a mechanism that positively controls NF-kappa B signalling via ubiquitin-mediated activation of DREDD. The direct involvement of ubiquitylation in caspase activation represents a novel mechanism for non-apoptotic caspase-mediated signalling.
    Original languageUndefined/Unknown
    Pages (from-to)2770–2783
    Number of pages14
    JournalEMBO Journal
    Volume31
    Issue number12
    DOIs
    Publication statusPublished - 2012
    MoE publication typeA1 Journal article-refereed

    Keywords

    • caspase
    • Drosophila
    • IAP
    • innate immunity
    • ubiquitin

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