Caspase Mediated Cleavage, IAP Binding and Ubiquitination: Linking Three Mechanisms Crucial for Drosophila NFKB Signaling

DAP-type PGN binding causes multimerization or clustering of PGRP receptors. This likely recruits the adapter proteins IMD, FADD and the caspase DREDD. Once in proximity, DREDD cleaves IMD, generating an exposed neo-N-terminal A31 residue. This neo-N-terminus then binds the E3 ligase DIAP2 via its BIR2/3 domains. In conjuction with the E2-ubiquitin conjugating enzymes UEV1a, Bendless (Ubc13) and Effete (Ubc5), IMD (and to a lesser degree DIAP2) are then K63-polyubiquitinated. These polyubiquitin chains then induce the activation of downstream kinases ultimately leading to the phosphorylation and activation of Relish and induction of downstream targets, like the AMP genes.

Publication

Caspase Mediated Cleavage, IAP Binding and Ubiquitination: Linking Three Mechanisms Crucial for Drosophila NF-κB Signaling. () Nicholas Paquette, et al. Mol Cell. ;37(2):172. Figure: F7. All organisms Drosophila melanogaster Mus musculus Homo sapiens Arabidopsis thaliana Danio rerio

Disease mentions