| http://purl.uniprot.org/citations/14713311 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/14713311 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/14713311 | http://www.w3.org/2000/01/rdf-schema#comment | "The identification of genetic mutations responsible for rare familial forms of Parkinson's disease (PD) have provided tremendous insight into the molecular pathogenesis of this disorder. Mutations in the DJ-1 gene cause autosomal recessive early onset PD in two European families. A Dutch kindred displays a large homozygous genomic deletion encompassing exons 1-5 of the DJ-1 gene, whereas an Italian kindred harbors a single homozygous L166P missense mutation. A homozygous M26I missense mutation was also recently reported in an Ashkenazi Jewish patient with early onset PD. Mutations in DJ-1 are predicted to be loss of function. The recent determination of the crystal structure of human DJ-1 demonstrates that it exists in a homo-dimeric form in vitro, whereas the L166P mutant exists only as a monomer. Here, we examine the in vivo effects of the pathogenic L166P and M26I mutations on the properties of DJ-1 in cell culture. We report that the L166P mutation confers markedly reduced protein stability to DJ-1, which results from enhanced degradation by the 20S/26S proteasome but not from a loss of mRNA expression. Furthermore, the L166P mutant protein exhibits an impaired ability to self-interact to form homo-oligomers. In contrast, the M26I mutation does not appear to adversely affect either protein stability, turnover by the proteasome, or the capacity of DJ-1 to form homo-oligomers. These properties of the L166P mutation may contribute to the loss of normal DJ-1 function and are likely to be the underlying cause of early onset PD in affected members of the Italian kindred."xsd:string |
| http://purl.uniprot.org/citations/14713311 | http://purl.org/dc/terms/identifier | "doi:10.1111/j.1471-4159.2003.02265.x"xsd:string |
| http://purl.uniprot.org/citations/14713311 | http://purl.org/dc/terms/identifier | "doi:10.1111/j.1471-4159.2003.02265.x"xsd:string |
| http://purl.uniprot.org/citations/14713311 | http://purl.uniprot.org/core/author | "Zhang L."xsd:string |
| http://purl.uniprot.org/citations/14713311 | http://purl.uniprot.org/core/author | "Zhang L."xsd:string |
| http://purl.uniprot.org/citations/14713311 | http://purl.uniprot.org/core/author | "Moore D.J."xsd:string |
| http://purl.uniprot.org/citations/14713311 | http://purl.uniprot.org/core/author | "Moore D.J."xsd:string |
| http://purl.uniprot.org/citations/14713311 | http://purl.uniprot.org/core/author | "Dawson T.M."xsd:string |
| http://purl.uniprot.org/citations/14713311 | http://purl.uniprot.org/core/author | "Dawson T.M."xsd:string |
| http://purl.uniprot.org/citations/14713311 | http://purl.uniprot.org/core/author | "Dawson V.L."xsd:string |
| http://purl.uniprot.org/citations/14713311 | http://purl.uniprot.org/core/author | "Dawson V.L."xsd:string |
| http://purl.uniprot.org/citations/14713311 | http://purl.uniprot.org/core/date | "2003"xsd:gYear |
| http://purl.uniprot.org/citations/14713311 | http://purl.uniprot.org/core/date | "2003"xsd:gYear |
| http://purl.uniprot.org/citations/14713311 | http://purl.uniprot.org/core/name | "J. Neurochem."xsd:string |
| http://purl.uniprot.org/citations/14713311 | http://purl.uniprot.org/core/name | "J. Neurochem."xsd:string |
| http://purl.uniprot.org/citations/14713311 | http://purl.uniprot.org/core/pages | "1558-1567"xsd:string |
| http://purl.uniprot.org/citations/14713311 | http://purl.uniprot.org/core/pages | "1558-1567"xsd:string |
| http://purl.uniprot.org/citations/14713311 | http://purl.uniprot.org/core/title | "A missense mutation (L166P) in DJ-1, linked to familial Parkinson's disease, confers reduced protein stability and impairs homo-oligomerization."xsd:string |
| http://purl.uniprot.org/citations/14713311 | http://purl.uniprot.org/core/title | "A missense mutation (L166P) in DJ-1, linked to familial Parkinson's disease, confers reduced protein stability and impairs homo-oligomerization."xsd:string |
| http://purl.uniprot.org/citations/14713311 | http://purl.uniprot.org/core/volume | "87"xsd:string |
| http://purl.uniprot.org/citations/14713311 | http://purl.uniprot.org/core/volume | "87"xsd:string |
| http://purl.uniprot.org/citations/14713311 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/14713311 |
| http://purl.uniprot.org/citations/14713311 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/14713311 |