| http://purl.uniprot.org/citations/29176737 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/29176737 | http://www.w3.org/2000/01/rdf-schema#comment | "Geographic atrophy is a blinding form of age-related macular degeneration characterized by retinal pigmented epithelium (RPE) death; the RPE also exhibits DICER1 deficiency, resultant accumulation of endogenous Alu-retroelement RNA, and NLRP3-inflammasome activation. How the inflammasome is activated in this untreatable disease is largely unknown. Here we demonstrate that RPE degeneration in human-cell-culture and mouse models is driven by a noncanonical-inflammasome pathway that activates caspase-4 (caspase-11 in mice) and caspase-1, and requires cyclic GMP-AMP synthase (cGAS)-dependent interferon-β production and gasdermin D-dependent interleukin-18 secretion. Decreased DICER1 levels or Alu-RNA accumulation triggers cytosolic escape of mitochondrial DNA, which engages cGAS. Moreover, caspase-4, gasdermin D, interferon-β, and cGAS levels were elevated in the RPE in human eyes with geographic atrophy. Collectively, these data highlight an unexpected role of cGAS in responding to mobile-element transcripts, reveal cGAS-driven interferon signaling as a conduit for mitochondrial-damage-induced inflammasome activation, expand the immune-sensing repertoire of cGAS and caspase-4 to noninfectious human disease, and identify new potential targets for treatment of a major cause of blindness."xsd:string |
| http://purl.uniprot.org/citations/29176737 | http://purl.org/dc/terms/identifier | "doi:10.1038/nm.4450"xsd:string |
| http://purl.uniprot.org/citations/29176737 | http://purl.uniprot.org/core/author | "Fukuda S."xsd:string |
| http://purl.uniprot.org/citations/29176737 | http://purl.uniprot.org/core/author | "Buxbaum J.D."xsd:string |
| http://purl.uniprot.org/citations/29176737 | http://purl.uniprot.org/core/author | "Kim Y."xsd:string |
| http://purl.uniprot.org/citations/29176737 | http://purl.uniprot.org/core/author | "Huang X."xsd:string |
| http://purl.uniprot.org/citations/29176737 | http://purl.uniprot.org/core/author | "Hara I."xsd:string |
| http://purl.uniprot.org/citations/29176737 | http://purl.uniprot.org/core/author | "Ogura Y."xsd:string |
| http://purl.uniprot.org/citations/29176737 | http://purl.uniprot.org/core/author | "Kajiwara Y."xsd:string |
| http://purl.uniprot.org/citations/29176737 | http://purl.uniprot.org/core/author | "West A.P."xsd:string |
| http://purl.uniprot.org/citations/29176737 | http://purl.uniprot.org/core/author | "Hirano Y."xsd:string |
| http://purl.uniprot.org/citations/29176737 | http://purl.uniprot.org/core/author | "Nagai H."xsd:string |
| http://purl.uniprot.org/citations/29176737 | http://purl.uniprot.org/core/author | "Fu D."xsd:string |
| http://purl.uniprot.org/citations/29176737 | http://purl.uniprot.org/core/author | "Terasaki H."xsd:string |
| http://purl.uniprot.org/citations/29176737 | http://purl.uniprot.org/core/author | "Banerjee D."xsd:string |
| http://purl.uniprot.org/citations/29176737 | http://purl.uniprot.org/core/author | "Fitzgerald K.A."xsd:string |
| http://purl.uniprot.org/citations/29176737 | http://purl.uniprot.org/core/author | "Kerur N."xsd:string |
| http://purl.uniprot.org/citations/29176737 | http://purl.uniprot.org/core/author | "Jazwinski S.M."xsd:string |
| http://purl.uniprot.org/citations/29176737 | http://purl.uniprot.org/core/author | "Cambier J.C."xsd:string |
| http://purl.uniprot.org/citations/29176737 | http://purl.uniprot.org/core/author | "Hinton D.R."xsd:string |
| http://purl.uniprot.org/citations/29176737 | http://purl.uniprot.org/core/author | "Sadda S.R."xsd:string |
| http://purl.uniprot.org/citations/29176737 | http://purl.uniprot.org/core/author | "Varshney A."xsd:string |
| http://purl.uniprot.org/citations/29176737 | http://purl.uniprot.org/core/author | "Kim K.B."xsd:string |
| http://purl.uniprot.org/citations/29176737 | http://purl.uniprot.org/core/author | "Leitinger N."xsd:string |