| http://purl.uniprot.org/citations/18577712 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18577712 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18577712 | http://www.w3.org/2000/01/rdf-schema#comment | "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-type pyrin. The N-terminal cleaved fragment interacted with the p65 subunit of NF-kappaB and with IkappaB-alpha through its 15-aa bZIP basic domain and adjacent sequences, respectively, and translocated to the nucleus. The interaction of the N-terminal fragment with p65 enhanced entrance of p65 into the nucleus. The interaction of N-terminal pyrin with IkappaB-alpha induced calpain-mediated degradation of IkappaB-alpha, thus potentiating NF-kappaB activation. Absolute and relative quantities of cleaved pyrin and IkappaB-alpha degradation products were substantially increased in leukocytes from FMF patients compared with healthy controls. Our data support a new pyrin/caspase-1 pathway for NF-kappaB activation."xsd:string |
| http://purl.uniprot.org/citations/18577712 | http://purl.org/dc/terms/identifier | "doi:10.1182/blood-2008-01-134932"xsd:string |
| http://purl.uniprot.org/citations/18577712 | http://purl.org/dc/terms/identifier | "doi:10.1182/blood-2008-01-134932"xsd:string |
| http://purl.uniprot.org/citations/18577712 | http://purl.uniprot.org/core/author | "Jaffe H."xsd:string |
| http://purl.uniprot.org/citations/18577712 | http://purl.uniprot.org/core/author | "Jaffe H."xsd:string |
| http://purl.uniprot.org/citations/18577712 | http://purl.uniprot.org/core/author | "Masters S.L."xsd:string |
| http://purl.uniprot.org/citations/18577712 | http://purl.uniprot.org/core/author | "Masters S.L."xsd:string |
| http://purl.uniprot.org/citations/18577712 | http://purl.uniprot.org/core/author | "Chae J.J."xsd:string |
| http://purl.uniprot.org/citations/18577712 | http://purl.uniprot.org/core/author | "Chae J.J."xsd:string |
| http://purl.uniprot.org/citations/18577712 | http://purl.uniprot.org/core/author | "Kastner D.L."xsd:string |
| http://purl.uniprot.org/citations/18577712 | http://purl.uniprot.org/core/author | "Kastner D.L."xsd:string |
| http://purl.uniprot.org/citations/18577712 | http://purl.uniprot.org/core/author | "Gumucio D.L."xsd:string |
| http://purl.uniprot.org/citations/18577712 | http://purl.uniprot.org/core/author | "Gumucio D.L."xsd:string |
| http://purl.uniprot.org/citations/18577712 | http://purl.uniprot.org/core/author | "Richard K."xsd:string |
| http://purl.uniprot.org/citations/18577712 | http://purl.uniprot.org/core/author | "Richard K."xsd:string |
| http://purl.uniprot.org/citations/18577712 | http://purl.uniprot.org/core/author | "Wood G."xsd:string |
| http://purl.uniprot.org/citations/18577712 | http://purl.uniprot.org/core/author | "Wood G."xsd:string |
| http://purl.uniprot.org/citations/18577712 | http://purl.uniprot.org/core/author | "Colburn N.T."xsd:string |
| http://purl.uniprot.org/citations/18577712 | http://purl.uniprot.org/core/author | "Colburn N.T."xsd:string |
| http://purl.uniprot.org/citations/18577712 | http://purl.uniprot.org/core/author | "Shoham N.G."xsd:string |
| http://purl.uniprot.org/citations/18577712 | http://purl.uniprot.org/core/author | "Shoham N.G."xsd:string |
| http://purl.uniprot.org/citations/18577712 | http://purl.uniprot.org/core/date | "2008"xsd:gYear |
| http://purl.uniprot.org/citations/18577712 | http://purl.uniprot.org/core/date | "2008"xsd:gYear |