USP7 and USP47 deubiquitinases regulate the NLRP3 inflammasome activation.

ABSTRACT: The assembly and activation of the inflammasomes are tightly regulated by post-translational modifications, including ubiquitin. Deubiquitinases counteract the addition of ubiquitin and are essential regulators of immune signalling pathways, including those acting on the inflammasome. How deubiquitinases control the assembly and activation of inflammasomes is unclear. Here we show that DUBs USP7 and USP47 regulate inflammasome activation in macrophages. Chemical inhibition of USP7 and USP47 blocks inflammasome formation, independently of transcription, by preventing ASC-oligomerisation and speck formation. We also provide evidence that the ubiquitination status of NLRP3 itself is altered by USP7 and USP47 inhibition. Interestingly, we found that the activity of USP7 and USP47 increased in

SUBMITTER: Dr. Pablo Palazon-Riquelme 

PROVIDER: S-SCDT-EMBOR-2017-44766V1 | biostudies-other |

REPOSITORIES: biostudies-other