| http://purl.uniprot.org/citations/24821797 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/24821797 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/24821797 | http://www.w3.org/2000/01/rdf-schema#comment | "A coding polymorphism (Thr300Ala) in the essential autophagy gene, autophagy related 16-like 1 (ATG16L1), confers increased risk for the development of Crohn disease, although the mechanisms by which single disease-associated polymorphisms contribute to pathogenesis have been difficult to dissect given that environmental factors likely influence disease initiation in these patients. Here we introduce a knock-in mouse model expressing the Atg16L1 T300A variant. Consistent with the human polymorphism, T300A knock-in mice do not develop spontaneous intestinal inflammation, but exhibit morphological defects in Paneth and goblet cells. Selective autophagy is reduced in multiple cell types from T300A knock-in mice compared with WT mice. The T300A polymorphism significantly increases caspase 3- and caspase 7-mediated cleavage of Atg16L1, resulting in lower levels of full-length Atg16Ll T300A protein. Moreover, Atg16L1 T300A is associated with decreased antibacterial autophagy and increased IL-1β production in primary cells and in vivo. Quantitative proteomics for protein interactors of ATG16L1 identified previously unknown nonoverlapping sets of proteins involved in ATG16L1-dependent antibacterial autophagy or IL-1β production. These findings demonstrate how the T300A polymorphism leads to cell type- and pathway-specific disruptions of selective autophagy and suggest a mechanism by which this polymorphism contributes to disease."xsd:string |
| http://purl.uniprot.org/citations/24821797 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1407001111"xsd:string |
| http://purl.uniprot.org/citations/24821797 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1407001111"xsd:string |
| http://purl.uniprot.org/citations/24821797 | http://purl.uniprot.org/core/author | "Daly M.J."xsd:string |
| http://purl.uniprot.org/citations/24821797 | http://purl.uniprot.org/core/author | "Daly M.J."xsd:string |
| http://purl.uniprot.org/citations/24821797 | http://purl.uniprot.org/core/author | "Heath R.J."xsd:string |
| http://purl.uniprot.org/citations/24821797 | http://purl.uniprot.org/core/author | "Heath R.J."xsd:string |
| http://purl.uniprot.org/citations/24821797 | http://purl.uniprot.org/core/author | "Mercer J."xsd:string |
| http://purl.uniprot.org/citations/24821797 | http://purl.uniprot.org/core/author | "Mercer J."xsd:string |
| http://purl.uniprot.org/citations/24821797 | http://purl.uniprot.org/core/author | "Virgin H.W."xsd:string |
| http://purl.uniprot.org/citations/24821797 | http://purl.uniprot.org/core/author | "Virgin H.W."xsd:string |
| http://purl.uniprot.org/citations/24821797 | http://purl.uniprot.org/core/author | "Jaffe J.D."xsd:string |
| http://purl.uniprot.org/citations/24821797 | http://purl.uniprot.org/core/author | "Jaffe J.D."xsd:string |
| http://purl.uniprot.org/citations/24821797 | http://purl.uniprot.org/core/author | "Xavier R.J."xsd:string |
| http://purl.uniprot.org/citations/24821797 | http://purl.uniprot.org/core/author | "Xavier R.J."xsd:string |
| http://purl.uniprot.org/citations/24821797 | http://purl.uniprot.org/core/author | "Becker C.E."xsd:string |
| http://purl.uniprot.org/citations/24821797 | http://purl.uniprot.org/core/author | "Becker C.E."xsd:string |
| http://purl.uniprot.org/citations/24821797 | http://purl.uniprot.org/core/author | "Becker M.L."xsd:string |
| http://purl.uniprot.org/citations/24821797 | http://purl.uniprot.org/core/author | "Becker M.L."xsd:string |
| http://purl.uniprot.org/citations/24821797 | http://purl.uniprot.org/core/author | "Bhan A.K."xsd:string |
| http://purl.uniprot.org/citations/24821797 | http://purl.uniprot.org/core/author | "Bhan A.K."xsd:string |
| http://purl.uniprot.org/citations/24821797 | http://purl.uniprot.org/core/author | "Carr S.A."xsd:string |
| http://purl.uniprot.org/citations/24821797 | http://purl.uniprot.org/core/author | "Carr S.A."xsd:string |