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Meinander, A., Runchel, C., Tenev, T., Chen, L., Kim, C.H., Ribeiro, P.S., Broemer, M., Leulier, F., Zvelebil, M., Silverman, N., Meier, P. (2012). Ubiquitylation of the initiator caspase DREDD is required for innate immune signalling.  EMBO J. 31(12): 2770--2783.
FlyBase ID
FBrf0218688
Publication Type
Research paper
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-κB (NF-κB). How caspases are activated under these conditions and process a selective set of substrates to allow NF-κB 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-κB/Relish and expression of antimicrobial peptide genes in response to infection with Gram-negative bacteria. Our results identify a mechanism that positively controls NF-κB 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.

PubMed ID
PubMed Central ID
PMC3380211 (PMC) (EuropePMC)
Related Publication(s)
Note

Innate immunity: regulation of caspases by IAP-dependent ubiquitylation.
Falschlehner and Boutros, 2012, EMBO J. 31(12): 2750--2752 [FBrf0219218]

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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    EMBO J.
    Title
    The EMBO Journal
    Publication Year
    1982-
    ISBN/ISSN
    0261-4189
    Data From Reference
    Alleles (14)
    Gene Groups (1)
    Genes (15)
    Physical Interactions (8)
    Cell Lines (1)
    Natural transposons (2)
    Insertions (1)
    Experimental Tools (1)
    Transgenic Constructs (7)