Functional degradation: A mechanism of NLRP1 inflammasome activation by diverse pathogen enzymes

In this study, we find that cleavage results in proteasome-mediated degradation of the amino-terminal domains of NLRP1B, liberating a carboxyl-terminal fragment that is a potent caspase-1 activator. Proteasome-mediated degradation of NLRP1B is both necessary and sufficient for NLRP1B activation. Consistent with our functional degradation model, we identify IpaH7.8, a Shigella flexneri ubiquitin ligase secreted effector, as an enzyme that induces NLRP1B degradation and activation. Our results provide a unified mechanism for NLRP1B activation by diverse pathogen-encoded enzymatic activities.

Source: ScienceNOW - April 3, 2019 Category: Science Authors: Sandstrom, A., Mitchell, P. S., Goers, L., Mu, E. W., Lesser, C. F., Vance, R. E. Tags: Immunology, Online Only r-articles Source Type: news