The familial Mediterranean fever protein, pyrin, is cleaved by caspase-1 and activates NF-kappa B through its N-terminal fragment
Jae Jin Chae, Geryl Wood, Katharina Richard, Howard Jaffe, Nona T Colburn, Seth L Masters, Deborah L Gumucio, Nitza G Shoham, Daniel L Kastner
BLOOD | AMER SOC HEMATOLOGY | Published : 2008
Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by mutations in MEFV, which encodes a 781-amino acid protein denoted pyrin. We have previously shown that pyrin regulates caspase-1 activation and IL-1beta production through interaction of its N-terminal PYD motif with the ASC adapter protein, and also modulates IL-1beta production by interaction of its C-terminal B30.2 domain with the catalytic domains of caspase-1. We now asked whether pyrin might itself be a caspase-1 substrate, and found that pyrin is cleaved by caspase-1 at Asp330, a site remote from the B30.2 domain. Pyrin variants harboring FMF-associated B30.2 mutations were cleaved more efficiently than wild-t..View full abstract
Awarded by NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
This work was supported by the Intramural Research Program of the National Institute of Arthritis and Muculoskeletal and Skill Diseases (Bethesda, MD).