Ubiquitylation of the initiator caspase DREDD is required for innate immune signalling
Department of Medicine, Division of Infectious Diseases and Immunology
Animals; Antimicrobial Cationic Peptides; Carrier Proteins; Caspases; Drosophila; Drosophila Proteins; *Gene Expression Regulation; Gram-Negative Bacteria; Immunity, Innate; Inhibitor of Apoptosis Proteins; Models, Biological; NF-kappa B; Transcription Factors; *Ubiquitination
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-kappaB (NF-kappaB). How caspases are activated under these conditions and process a selective set of substrates to allow NF-kappaB 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-kappaB/Relish and expression of antimicrobial peptide genes in response to infection with Gram-negative bacteria. Our results identify a mechanism that positively controls NF-kappaB 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.
Meinander, Annika; Runchel, Christopher; Tenev, Tencho; Chen, Li; Kim, Chan-Hee; Ribeiro, Paulo S.; Broemer, Meike; Leulier, Francois; Zvelebil, Marketa; Silverman, Neal S.; and Meier, Pascal, "Ubiquitylation of the initiator caspase DREDD is required for innate immune signalling" (2012). Infectious Diseases and Immunology Publications and Presentations. 152.