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Ubiquitylation of the initiator caspase DREDD is required for innate immune signalling
Infectious Diseases and Immunology Publications and Presentations
  • Annika Meinander, Abo Akademi University
  • Christopher Runchel, Chester Beatty Laboratories
  • Tencho Tenev, Chester Beatty Laboratories
  • Li Chen, University of Massachusetts Medical School
  • Chan-Hee Kim, University of Massachusetts Medical School
  • Paulo S. Ribeiro, London Research Institute
  • Meike Broemer, Breakthrough Toby Robins Breast Cancer Research Centre
  • Francois Leulier, Breakthrough Toby Robins Breast Cancer Research Centre
  • Marketa Zvelebil, Chester Beatty Laboratories
  • Neal S. Silverman, University of Massachusetts Medical School
  • Pascal Meier, Breakthrough Toby Robins Breast Cancer Research Centre
UMMS Affiliation
Department of Medicine, Division of Infectious Diseases and Immunology
Date
5-1-2012
Document Type
Article
Subjects
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
Abstract
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.
Comments

Citation: EMBO J. 2012 May 1;31(12):2770-83. doi: 10.1038/emboj.2012.121. Link to article on publisher's site

Related Resources
Link to Article in PubMed
PubMed ID
22549468
Citation Information
Annika 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/