Caspase-Mediated Cleavage, IAP Binding, and Ubiquitination: Linking Three Mechanisms Crucial for Drosophila NF-κB SignalingInfectious Diseases and Immunology Publications and Presentations
UMMS AffiliationDepartment of Medicine, Division of Infectious Diseases and Immunology
SubjectsImmunity, Innate; Drosophila; Intracellular Signaling Peptides and Proteins; Signal Transduction; DNA Cleavage; Caspases; Inhibitor of Apoptosis Proteins; Ubiquitination
AbstractInnate 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 PermissionsCitation: 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 ResourcesLink to article in PubMed
Citation InformationNicholas 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/