| http://purl.uniprot.org/citations/26968342 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26968342 | http://www.w3.org/2000/01/rdf-schema#comment | "Sepsis is burdened by high mortality due to uncontrolled inflammatory response to pathogens. Increased caspase 1 activation causing maturation of IL1β/18 remains a therapeutic challenge in sepsis. SHARPIN (shank-associated regulator of G-protein signaling homology domain-interacting protein), a component of the LUBAC (linear ubiquitin chain-assembly complex), regulates inflammation, with unknown effects on caspase 1 activation. Mice lacking Casp1, Casp11, or both in a Sharpin-deficient background were generated, exposed to lipopolysaccharide-induced endotoxemia, and injected with caspase 1 inhibitor. We monitored survival, Il1β/18, and caspase 1/11 levels in plasma and organs and deciphered mechanisms of SHARPIN-dependent caspase 1 inhibition. A correlation between LUBAC and active caspase 1 was found in blood mononuclear cells from septic patients. SHARPIN bound caspase 1 and disrupted p20/p10 dimer formation, the last step of caspase 1 processing, thereby inhibiting enzyme activation and maturation of IL1β/18 in a LUBAC-independent manner. In septic patients, LUBAC-independent decline in SHARPIN correlated with enhancement of active caspase 1 in circulating mononuclear cells. Septic Sharpin-deficient mice displayed enrichment in mature Il1β/18 and active caspase 1, and shortened survival. Inhibition of caspase 1 reduced levels of Il1β/18 and splenic cell death, and prolonged survival in septic Sharpin-deficient mice. Our findings identify SHARPIN as a potent in vivo caspase 1 inhibitor and propose the caspase 1-SHARPIN interaction as a target in sepsis."xsd:string |
| http://purl.uniprot.org/citations/26968342 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.ajpath.2015.12.026"xsd:string |
| http://purl.uniprot.org/citations/26968342 | http://purl.uniprot.org/core/author | "Schaefer L."xsd:string |
| http://purl.uniprot.org/citations/26968342 | http://purl.uniprot.org/core/author | "Dikic I."xsd:string |
| http://purl.uniprot.org/citations/26968342 | http://purl.uniprot.org/core/author | "Ikeda F."xsd:string |
| http://purl.uniprot.org/citations/26968342 | http://purl.uniprot.org/core/author | "Pfeilschifter J."xsd:string |
| http://purl.uniprot.org/citations/26968342 | http://purl.uniprot.org/core/author | "Lopez-Mosqueda J."xsd:string |
| http://purl.uniprot.org/citations/26968342 | http://purl.uniprot.org/core/author | "Iozzo R.V."xsd:string |
| http://purl.uniprot.org/citations/26968342 | http://purl.uniprot.org/core/author | "Beckmann J."xsd:string |
| http://purl.uniprot.org/citations/26968342 | http://purl.uniprot.org/core/author | "Schroeder N."xsd:string |
| http://purl.uniprot.org/citations/26968342 | http://purl.uniprot.org/core/author | "Frey H."xsd:string |
| http://purl.uniprot.org/citations/26968342 | http://purl.uniprot.org/core/author | "Mersmann J."xsd:string |
| http://purl.uniprot.org/citations/26968342 | http://purl.uniprot.org/core/author | "Zeng-Brouwers J."xsd:string |
| http://purl.uniprot.org/citations/26968342 | http://purl.uniprot.org/core/author | "Poluzzi C."xsd:string |
| http://purl.uniprot.org/citations/26968342 | http://purl.uniprot.org/core/author | "Nastase M.V."xsd:string |
| http://purl.uniprot.org/citations/26968342 | http://purl.uniprot.org/core/author | "Hsieh L.T."xsd:string |
| http://purl.uniprot.org/citations/26968342 | http://purl.uniprot.org/core/date | "2016"xsd:gYear |
| http://purl.uniprot.org/citations/26968342 | http://purl.uniprot.org/core/name | "Am J Pathol"xsd:string |
| http://purl.uniprot.org/citations/26968342 | http://purl.uniprot.org/core/pages | "1206-1220"xsd:string |
| http://purl.uniprot.org/citations/26968342 | http://purl.uniprot.org/core/title | "An Essential Role for SHARPIN in the Regulation of Caspase 1 Activity in Sepsis."xsd:string |
| http://purl.uniprot.org/citations/26968342 | http://purl.uniprot.org/core/volume | "186"xsd:string |
| http://purl.uniprot.org/citations/26968342 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/26968342 |
| http://purl.uniprot.org/citations/26968342 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/26968342 |
| http://purl.uniprot.org/uniprot/#_E0CZH2-mappedCitation-26968342 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26968342 |