DPP9 sequesters the C terminus of NLRP1 to repress inflammasome activation.

ABSTRACT: Nucleotide-binding domain and leucine-rich repeat pyrin-domain containing protein 1 (NLRP1) is an inflammasome sensor that mediates the activation of caspase-1 to induce cytokine maturation and pyroptosis^1-4. Gain-of-function mutations of NLRP1 cause severe inflammatory diseases of the skin^4-6. NLRP1 contains a function-to-find domain that auto-proteolyses into noncovalently associated subdomains^7-9, and proteasomal degradation of the repressive N-terminal fragment of NLRP1 releases its inflammatory C-terminal fragment (NLRP1 CT)^10,11. Cytosolic dipeptidyl peptidases 8 and 9 (hereafter, DPP8/DPP9) both interact with NLRP1, and small-molecule inhibitors of DPP8/DPP9 activate NLRP1 by mechanisms that are currently unclear^10,12-14. Here w

SUBMITTER: Hollingsworth LR 

PROVIDER: S-EPMC8299537 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature