Ubiquitylation of the initiator caspase DREDD is required for innate immune signallingInfectious Diseases and Immunology Publications and Presentations
UMMS AffiliationDepartment of Medicine, Division of Infectious Diseases and Immunology
SubjectsAnimals; 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
AbstractCaspases 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.
Related ResourcesLink to Article in PubMed
Citation InformationAnnika Meinander, Christopher Runchel, Tencho Tenev, Li Chen, et al.. "Ubiquitylation of the initiator caspase DREDD is required for innate immune signalling" Vol. 31 Iss. 12 (2012) ISSN: 0261-4189 (Linking)
Available at: http://works.bepress.com/neal_silverman/52/