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

作者：Meinander Annika; Runchel Christopher; Tenev Tencho; Chen Li; Kim Chan Hee; Ribeiro Paulo S; Broemer Meike; Leulier Francois; Zvelebil Marketa; Silverman Neal; Meier Pascal^*

来源：The EMBO Journal, 2012, 31(12): 2770-2783.

DOI：10.1038/emboj.2012.121

• caspase
• Drosophila
• IAP
• innate immunity
• ubiquitin

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. The EMBO Journal (2012) 31, 2770-2783. doi:10.1038/emboj.2012.121; Published online 1 May 2012

• 出版日期2012-6-13