PLK4 deubiquitination by Spata2-CYLD suppresses NEK7-mediated NLRP3 inflammasome activation at the centrosome

ABSTRACT: The innate immune sensor NLRP3 assembles an inflammasome complex with NEK7 and ASC to activate Caspase-1 and drive the maturation of proinflammatory cytokines IL-1beta and IL-18. The NLRP3 inflammasome activity must be tightly controlled because its over-activation is implicated in the pathogenesis of inflammatory diseases. Here we show that NLRP3 inflammasome activation is suppressed by a centrosomal protein Spata2. Spata2 deficiency enhances the NLRP3 inflammasome activity both in macrophages and in an animal model of peritonitis. Mechanistically, Spata2 recruits CYLD to the centrosome where they deubiquitinate polo-like kinase 4 (PLK4), a key regulator of centrosome duplication, to facilitate its binding to and phosphorylation of NEK7 at Ser204. NEK7 phosphorylation in turn attenuates

SUBMITTER: Bing Su 

PROVIDER: S-SCDT-EMBOJ-2019-102201 | biostudies-other |

REPOSITORIES: biostudies-other