| http://purl.uniprot.org/citations/14684739 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/14684739 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/14684739 | http://www.w3.org/2000/01/rdf-schema#comment | "Approximately 20% of familial amyotrophic lateral sclerosis (FALS) arises from germ-line mutations in the superoxide dismutase-1 (SOD1) gene. However, the molecular mechanisms underlying the process have been elusive. Here, we show that a neuronal homologous to E6AP carboxyl terminus (HECT)-type ubiquitin-protein isopeptide ligase (NEDL1) physically binds translocon-associated protein-delta and also binds and ubiquitinates mutant (but not wild-type) SOD1 proportionately to the disease severity caused by that particular mutant. Immunohistochemically, NEDL1 is present in the central region of the Lewy body-like hyaline inclusions in the spinal cord ventral horn motor neurons of both FALS patients and mutant SOD1 transgenic mice. Two-hybrid screening for the physiological targets of NEDL1 has identified Dishevelled-1, one of the key transducers in the Wnt signaling pathway. Mutant SOD1 also interacted with Dishevelled-1 in the presence of NEDL1 and caused its dysfunction. Thus, our results suggest that an adverse interaction among misfolded SOD1, NEDL1, translocon-associated protein-delta, and Dishevelled-1 forms a ubiquitinated protein complex that is included in potentially cytotoxic protein aggregates and that mutually affects their functions, leading to motor neuron death in FALS."xsd:string |
| http://purl.uniprot.org/citations/14684739 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m312389200"xsd:string |
| http://purl.uniprot.org/citations/14684739 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m312389200"xsd:string |
| http://purl.uniprot.org/citations/14684739 | http://purl.uniprot.org/core/author | "Aoki M."xsd:string |
| http://purl.uniprot.org/citations/14684739 | http://purl.uniprot.org/core/author | "Aoki M."xsd:string |
| http://purl.uniprot.org/citations/14684739 | http://purl.uniprot.org/core/author | "Goto T."xsd:string |
| http://purl.uniprot.org/citations/14684739 | http://purl.uniprot.org/core/author | "Goto T."xsd:string |
| http://purl.uniprot.org/citations/14684739 | http://purl.uniprot.org/core/author | "Itoyama Y."xsd:string |
| http://purl.uniprot.org/citations/14684739 | http://purl.uniprot.org/core/author | "Itoyama Y."xsd:string |
| http://purl.uniprot.org/citations/14684739 | http://purl.uniprot.org/core/author | "Kato S."xsd:string |
| http://purl.uniprot.org/citations/14684739 | http://purl.uniprot.org/core/author | "Kato S."xsd:string |
| http://purl.uniprot.org/citations/14684739 | http://purl.uniprot.org/core/author | "Kato C."xsd:string |
| http://purl.uniprot.org/citations/14684739 | http://purl.uniprot.org/core/author | "Kato C."xsd:string |
| http://purl.uniprot.org/citations/14684739 | http://purl.uniprot.org/core/author | "Fujita T."xsd:string |
| http://purl.uniprot.org/citations/14684739 | http://purl.uniprot.org/core/author | "Fujita T."xsd:string |
| http://purl.uniprot.org/citations/14684739 | http://purl.uniprot.org/core/author | "Ozaki T."xsd:string |
| http://purl.uniprot.org/citations/14684739 | http://purl.uniprot.org/core/author | "Ozaki T."xsd:string |
| http://purl.uniprot.org/citations/14684739 | http://purl.uniprot.org/core/author | "Sakamoto M."xsd:string |
| http://purl.uniprot.org/citations/14684739 | http://purl.uniprot.org/core/author | "Sakamoto M."xsd:string |
| http://purl.uniprot.org/citations/14684739 | http://purl.uniprot.org/core/author | "Miyazaki K."xsd:string |
| http://purl.uniprot.org/citations/14684739 | http://purl.uniprot.org/core/author | "Miyazaki K."xsd:string |
| http://purl.uniprot.org/citations/14684739 | http://purl.uniprot.org/core/author | "Nakagawara A."xsd:string |
| http://purl.uniprot.org/citations/14684739 | http://purl.uniprot.org/core/author | "Nakagawara A."xsd:string |