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Caspase-Mediated Cleavage, IAP Binding, and Ubiquitination: Linking Three Mechanisms Crucial for Drosophila NF-κB Signaling
Infectious Diseases and Immunology Publications and Presentations
  • Nicholas Paul Paquette, University of Massachusetts Medical School
  • Meike Broemer, Breakthrough Toby Robins Breast Cancer Resaearch Centre
  • Kamna Aggarwal, University of Massachusetts Medical School
  • Li Chen, University of Massachusetts Medical School
  • Marie Husson, Universite de Strasbourg
  • Deniz Erturk Hasdemir, University of Massachusetts Medical School
  • Jean-Marc Reichhart, Universite de Strasbourg
  • Pascal Meier, Breakthrough Toby Robins Breast Cancer Resaearch Centre
  • Neal S. Silverman, University of Massachusetts Medical School
UMMS Affiliation
Department of Medicine, Division of Infectious Diseases and Immunology
Date
1-28-2010
Document Type
Article
Subjects
Immunity, Innate; Drosophila; Intracellular Signaling Peptides and Proteins; Signal Transduction; DNA Cleavage; Caspases; Inhibitor of Apoptosis Proteins; Ubiquitination
Abstract
Innate immune responses are critical for the immediate protection against microbial infection. In Drosophila, infection leads to the rapid and robust production of antimicrobial peptides through two NF-κB signaling pathways—IMD and Toll. The IMD pathway is triggered by DAP-type peptidoglycan, common to most Gram-negative bacteria. Signaling downstream from the peptidoglycan receptors is thought to involve K63 ubiquitination and caspase-mediated cleavage, but the molecular mechanisms remain obscure. We now show that PGN stimulation causes caspase-mediated cleavage of the imd protein, exposing a highly conserved IAP-binding motif (IBM) at its neo-N terminus. A functional IBM is required for the association of cleaved IMD with the ubiquitin E3-ligase DIAP2. Through its association with DIAP2, IMD is rapidly conjugated with K63-linked polyubiquitin chains. These results mechanistically connect caspase-mediated cleavage and K63 ubiquitination in immune-induced NF-κB signaling.
Rights and Permissions
Citation: Nicholas Paquette, Meike Broemer, Kamna Aggarwal, Li Chen, Marie Husson, Deniz Erturk-Hasdemir, Jean-Marc Reichhart, Pascal Meier, Neal Silverman. Caspase-Mediated Cleavage, IAP Binding, and Ubiquitination: Linking Three Mechanisms Crucial for Drosophila NF-[kappa]B Signaling. Molecular Cell, Volume 37, Issue 2, 29 January 2010, Pages 172-182. Link to article on publisher's website
Related Resources
Link to article in PubMed
PubMed ID
20122400
Citation Information
Nicholas Paul Paquette, Meike Broemer, Kamna Aggarwal, Li Chen, et al.. "Caspase-Mediated Cleavage, IAP Binding, and Ubiquitination: Linking Three Mechanisms Crucial for Drosophila NF-κB Signaling" Vol. 37 Iss. 2 (2010)
Available at: http://works.bepress.com/neal_silverman/45/