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

A1 Journal article (refereed)

Internal Authors/Editors

Publication Details

List of Authors: Meinander A, Runchel C, Tenev T, Chen L, Kim CH, Ribeiro PS, Broemer M, Leulier F, Zvelebil M, Silverman N, Meier P
Publisher: Wiley-Blackwell Publishing
Publication year: 2012
Journal: EMBO Journal
Journal acronym: EMBO J
Volume number: 31
Issue number: 12
Start page: 2770
End page: 2783
Number of pages: 14
ISSN: 0261-4189
eISSN: 1460-2075


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.


caspase, Drosophila, IAP, innate immunity, ubiquitin

Last updated on 2020-21-09 at 04:51