| http://purl.uniprot.org/citations/16785446 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/16785446 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/16785446 | http://www.w3.org/2000/01/rdf-schema#comment | "Familial Mediterranean fever (FMF) is a recessively inherited autoinflammatory disorder with high carrier frequencies in the Middle East. Pyrin, the protein mutated in FMF, regulates caspase-1 activation and consequently IL-1beta production through cognate interaction of its N-terminal PYRIN motif with the ASC adaptor protein. However, the preponderance of mutations reside in pyrin's C-terminal B30.2 domain. Here we demonstrate direct interaction of this domain with caspase-1. In lysates from cells not expressing ASC, reciprocal GST pull-downs demonstrated the interaction of pyrin with the p20 and p10 catalytic subunits of caspase-1. Coimmunoprecipitations of pyrin and caspase-1 from THP-1 human monocytic cells were consistent with the interaction of endogenous proteins. The C-terminal B30.2 domain of pyrin is necessary and sufficient for the interaction, and binding was reduced by FMF-associated B30.2 mutations. Full-length pyrin attenuated IL-1beta production in cells transfected with a caspase-1/IL-1beta construct, an effect diminished by FMF-associated B30.2 mutations and in B30.2 deletion mutants. Modeling of the crystal structure of caspase-1 with the deduced structure of the pyrin B30.2 domain corroborated both the interaction and the importance of M694V and M680I pyrin mutations. Consistent with a net inhibitory effect of pyrin on IL-1beta activation, small interfering RNA (siRNA)-mediated pyrin knockdown in THP-1 cells augmented IL-1beta production in response to bacterial LPS. Moreover, the IL-1 receptor antagonist anakinra suppressed acute-phase proteins in a patient with FMF and amyloidosis. Our data support a direct, ASC-independent effect of pyrin on IL-1beta activation and suggest heightened IL-1 responsiveness as one factor selecting for pyrin mutations."xsd:string |
| http://purl.uniprot.org/citations/16785446 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.0602081103"xsd:string |
| http://purl.uniprot.org/citations/16785446 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.0602081103"xsd:string |
| http://purl.uniprot.org/citations/16785446 | http://purl.uniprot.org/core/author | "Masters S.L."xsd:string |
| http://purl.uniprot.org/citations/16785446 | http://purl.uniprot.org/core/author | "Masters S.L."xsd:string |
| http://purl.uniprot.org/citations/16785446 | http://purl.uniprot.org/core/author | "Smith B.J."xsd:string |
| http://purl.uniprot.org/citations/16785446 | http://purl.uniprot.org/core/author | "Smith B.J."xsd:string |
| http://purl.uniprot.org/citations/16785446 | http://purl.uniprot.org/core/author | "Park G."xsd:string |
| http://purl.uniprot.org/citations/16785446 | http://purl.uniprot.org/core/author | "Park G."xsd:string |
| http://purl.uniprot.org/citations/16785446 | http://purl.uniprot.org/core/author | "Chae J.J."xsd:string |
| http://purl.uniprot.org/citations/16785446 | http://purl.uniprot.org/core/author | "Chae J.J."xsd:string |
| http://purl.uniprot.org/citations/16785446 | http://purl.uniprot.org/core/author | "Kastner D.L."xsd:string |
| http://purl.uniprot.org/citations/16785446 | http://purl.uniprot.org/core/author | "Kastner D.L."xsd:string |
| http://purl.uniprot.org/citations/16785446 | http://purl.uniprot.org/core/author | "Richard K."xsd:string |
| http://purl.uniprot.org/citations/16785446 | http://purl.uniprot.org/core/author | "Richard K."xsd:string |
| http://purl.uniprot.org/citations/16785446 | http://purl.uniprot.org/core/author | "Wood G."xsd:string |
| http://purl.uniprot.org/citations/16785446 | http://purl.uniprot.org/core/author | "Wood G."xsd:string |
| http://purl.uniprot.org/citations/16785446 | http://purl.uniprot.org/core/date | "2006"xsd:gYear |
| http://purl.uniprot.org/citations/16785446 | http://purl.uniprot.org/core/date | "2006"xsd:gYear |
| http://purl.uniprot.org/citations/16785446 | http://purl.uniprot.org/core/name | "Proc. Natl. Acad. Sci. U.S.A."xsd:string |
| http://purl.uniprot.org/citations/16785446 | http://purl.uniprot.org/core/name | "Proc. Natl. Acad. Sci. U.S.A."xsd:string |
| http://purl.uniprot.org/citations/16785446 | http://purl.uniprot.org/core/pages | "9982-9987"xsd:string |
| http://purl.uniprot.org/citations/16785446 | http://purl.uniprot.org/core/pages | "9982-9987"xsd:string |