The N-end rule ubiquitin ligase UBR2 mediates NLRP1B inflammasome activation by anthrax lethal toxin

ABSTRACT: Anthrax lethal toxin (LT) is known to induce NLRP1B inflammasome activation and pyroptotic cell death in macrophages from certain mouse strains in its metalloprotease activity-dependent manner, but the underlying mechanism is unknown. Here we establish a simple but robust cell system bearing dual fluorescence reporters for LT-induced ASC specks formation and pyroptotic lysis. A genome-wide siRNA screen and a CRISPR-Cas9 knockout screen were applied to this system for identifying genes involved in LT-induced inflammasome activation. UBR2, an E3 ubiquitin ligase of the N-end rule degradation pathway, was found to be required for LT-induced NLRP1B inflammasome activation. LT is known to cleave NLRP1B after Lys-44. The cleaved NLRP1B, bearing an N-terminal leucine, was targeted by UBR2-mediate

SUBMITTER: Dr. Feng Shao 

PROVIDER: S-SCDT-95246_1_1559722941_jats | biostudies-other |

REPOSITORIES: biostudies-other