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-kappaB 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-kappaB signaling.
journal_name
Mol Celljournal_title
Molecular cellauthors
Paquette N,Broemer M,Aggarwal K,Chen L,Husson M,Ertürk-Hasdemir D,Reichhart JM,Meier P,Silverman Ndoi
10.1016/j.molcel.2009.12.036subject
Has Abstractpub_date
2010-01-29 00:00:00pages
172-82issue
2eissn
1097-2765issn
1097-4164pii
S1097-2765(10)00039-0journal_volume
37pub_type
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