PMID:23152930

Citation	Hellmich, KA, Levinsohn, JL, Fattah, R, Newman, ZL, Maier, N, Sastalla, I, Liu, S, Leppla, SH and Moayeri, M (2012) Anthrax lethal factor cleaves mouse nlrp1b in both toxin-sensitive and toxin-resistant macrophages. PLoS ONE 7:e49741
Abstract	Anthrax lethal factor (LF) is the protease component of anthrax lethal toxin (LT). LT induces pyroptosis in macrophages of certain inbred mouse and rat strains, while macrophages from other inbred strains are resistant to the toxin. In rats, the sensitivity of macrophages to toxin-induced cell death is determined by the presence of an LF cleavage sequence in the inflammasome sensor Nlrp1. LF cleaves rat Nlrp1 of toxin-sensitive macrophages, activating caspase-1 and inducing cell death. Toxin-resistant macrophages, however, express Nlrp1 proteins which do not harbor the LF cleavage site. We report here that mouse Nlrp1b proteins are also cleaved by LF. In contrast to the situation in rats, sensitivity and resistance of Balb/cJ and NOD/LtJ macrophages does not correlate to the susceptibility of their Nlrp1b proteins to cleavage by LF, as both proteins are cleaved. Two LF cleavage sites, at residues 38 and 44, were identified in mouse Nlrp1b. Our results suggest that the resistance of NOD/LtJ macrophages to LT, and the inability of the Nlrp1b protein expressed in these cells to be activated by the toxin are likely due to polymorphisms other than those at the LF cleavage sites.
Links	PubMed Online version:10.1371/journal.pone.0049741
Keywords
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
BACAN:LEF	involved_in	GO:0006508: proteolysis	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
BACAN:LEF		GO:0006508: proteolysis	ECO:0000314:		P		Figure 2 and 3	complete CACAO 6047

References

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