Title : N-terminal degradation activates the NLRP1B inflammasome - Chui_2019_Science_364_82 |
Author(s) : Chui AJ , Okondo MC , Rao SD , Gai K , Griswold AR , Johnson DC , Ball DP , Taabazuing CY , Orth EL , Vittimberga BA , Bachovchin DA |
Ref : Science , 364 :82 , 2019 |
Abstract :
Intracellular pathogens and danger signals trigger the formation of inflammasomes, which activate inflammatory caspases and induce pyroptosis. The anthrax lethal factor metalloprotease and small-molecule DPP8/9 inhibitors both activate the NLRP1B inflammasome, but the molecular mechanism of NLRP1B activation is unknown. 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. |
PubMedSearch : Chui_2019_Science_364_82 |
PubMedID: 30872531 |
Chui AJ, Okondo MC, Rao SD, Gai K, Griswold AR, Johnson DC, Ball DP, Taabazuing CY, Orth EL, Vittimberga BA, Bachovchin DA (2019)
N-terminal degradation activates the NLRP1B inflammasome
Science
364 :82
Chui AJ, Okondo MC, Rao SD, Gai K, Griswold AR, Johnson DC, Ball DP, Taabazuing CY, Orth EL, Vittimberga BA, Bachovchin DA (2019)
Science
364 :82