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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/32241

Title: Proteolytic Processing of Nlrp1b in the FIIND Domain is Required for Inflammasome Activity
Authors: Frew, Bradley
Advisor: Mogridge, Jeremy
Department: Laboratory Medicine and Pathobiology
Keywords: Microbiology
Immunology
Nlrp1b
Nalp1b
Inflammasome
Anthrax
Lethal toxin
pyroptosis
caspase-1
NLR
Nlrp1
IL-1
NOD
CARD8
Cleaved
Cleavage
Proteolysis
Innate immune
Pattern recognition receptor
Inflammation
FIIND
CARD
Issue Date: 21-Mar-2012
Abstract: Nlrp1b is a NOD-like receptor of the innate immune system that upon sensing of anthrax lethal toxin oliogmerizes and forms a protein scaffold that binds to and activates pro-caspase-1; this complex is called an inflammasome. Nlrp1b is highly polymorphic and different alleles display an all or none ability to sense lethal toxin. Here I show that Nlrp1b is cleaved in the FIIND domain, and that the cleaved fragments remain associated even after activation by lethal toxin. The inflammasome activity of an inactive allele was restored by three mutations, one of which also restored cleavage. A heterologous cleavage site was inserted into an uncleaved mutant of Nlrp1b; induced proteolysis of the cleavage site rescued inflammasome activity. An uncleaved mutant of Nlrp1b showed no deficiency in FIIND self-association, but did have reduced recruitment of pro-caspase-1. These data provide evidence that cleavage of Nlrp1b is required for proper recruitment and activation of caspase-1.
URI: http://hdl.handle.net/1807/32241
Appears in Collections:Master

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