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.

FBrf0218688

Research paper

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.

PMC3380211 (PMC) (EuropePMC)