N-terminal degradation activates the NLRP1B inflammasome
In this study, we used genome-wide CRISPR-Cas9 knockout screens to identify genes required for NLRP1B-mediated pyroptosis. We discovered that lethal factor induces cell death via the N-end rule proteasomal degradation pathway. Lethal factor directly cleaves NLRP1B, inducing the N-end rule–mediated degradation of the NLRP1B N terminus and freeing the NLRP1B C terminus to activate caspase-1. DPP8/9 inhibitors also induce proteasomal degradation of the NLRP1B N terminus but not via the N-end rule pathway. Thus, N-terminal degradation is the common activation mechanism of this innate immune sensor.
Source: ScienceNOW - Category: Science Authors: Chui, A. J., Okondo, M. C., Rao, S. D., Gai, K., Griswold, A. R., Johnson, D. C., Ball, D. P., Taabazuing, C. Y., Orth, E. L., Vittimberga, B. A., Bachovchin, D. A. Tags: Immunology reports Source Type: news