| http://purl.uniprot.org/citations/12660785 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/12660785 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/12660785 | http://www.w3.org/2000/01/rdf-schema#comment | "Mutations in presenilin genes account for the majority of the cases of the familial form of Alzheimer's disease (FAD). Presenilin is essential for gamma-secretase activity, a proteolytic activity involved in intramembrane cleavage of Notch and beta-amyloid precursor protein (betaAPP). Cleavage of betaAPP by FAD mutant presenilin results in the overproduction of highly amyloidogenic amyloid beta42 peptides. gamma-Secretase activity requires the formation of a stable, high-molecular-mass protein complex that, in addition to the endoproteolysed fragmented form of presenilin, contains essential cofactors including nicastrin, APH-1 (refs 15-18) and PEN-2 (refs 16, 19). However, the role of each protein in complex formation and the generation of enzymatic activity is unclear. Here we show that Drosophila APH-1 (Aph-1) increases the stability of Drosophila presenilin (Psn) holoprotein in the complex. Depletion of PEN-2 by RNA interference prevents endoproteolysis of presenilin and promotes stabilization of the holoprotein in both Drosophila and mammalian cells, including primary neurons. Co-expression of Drosophila Pen-2 with Aph-1 and nicastrin increases the formation of Psn fragments as well as gamma-secretase activity. Thus, APH-1 stabilizes the presenilin holoprotein in the complex, whereas PEN-2 is required for endoproteolytic processing of presenilin and conferring gamma-secretase activity to the complex."xsd:string |
| http://purl.uniprot.org/citations/12660785 | http://purl.org/dc/terms/identifier | "doi:10.1038/nature01506"xsd:string |
| http://purl.uniprot.org/citations/12660785 | http://purl.org/dc/terms/identifier | "doi:10.1038/nature01506"xsd:string |
| http://purl.uniprot.org/citations/12660785 | http://purl.uniprot.org/core/author | "Takahashi Y."xsd:string |
| http://purl.uniprot.org/citations/12660785 | http://purl.uniprot.org/core/author | "Takahashi Y."xsd:string |
| http://purl.uniprot.org/citations/12660785 | http://purl.uniprot.org/core/author | "Tomita T."xsd:string |
| http://purl.uniprot.org/citations/12660785 | http://purl.uniprot.org/core/author | "Tomita T."xsd:string |
| http://purl.uniprot.org/citations/12660785 | http://purl.uniprot.org/core/author | "Iwatsubo T."xsd:string |
| http://purl.uniprot.org/citations/12660785 | http://purl.uniprot.org/core/author | "Iwatsubo T."xsd:string |
| http://purl.uniprot.org/citations/12660785 | http://purl.uniprot.org/core/author | "Thinakaran G."xsd:string |
| http://purl.uniprot.org/citations/12660785 | http://purl.uniprot.org/core/author | "Thinakaran G."xsd:string |
| http://purl.uniprot.org/citations/12660785 | http://purl.uniprot.org/core/author | "Hayashi I."xsd:string |
| http://purl.uniprot.org/citations/12660785 | http://purl.uniprot.org/core/author | "Hayashi I."xsd:string |
| http://purl.uniprot.org/citations/12660785 | http://purl.uniprot.org/core/author | "Niimura M."xsd:string |
| http://purl.uniprot.org/citations/12660785 | http://purl.uniprot.org/core/author | "Niimura M."xsd:string |
| http://purl.uniprot.org/citations/12660785 | http://purl.uniprot.org/core/author | "Takasugi N."xsd:string |
| http://purl.uniprot.org/citations/12660785 | http://purl.uniprot.org/core/author | "Takasugi N."xsd:string |
| http://purl.uniprot.org/citations/12660785 | http://purl.uniprot.org/core/author | "Tsuruoka M."xsd:string |
| http://purl.uniprot.org/citations/12660785 | http://purl.uniprot.org/core/author | "Tsuruoka M."xsd:string |
| http://purl.uniprot.org/citations/12660785 | http://purl.uniprot.org/core/date | "2003"xsd:gYear |
| http://purl.uniprot.org/citations/12660785 | http://purl.uniprot.org/core/date | "2003"xsd:gYear |
| http://purl.uniprot.org/citations/12660785 | http://purl.uniprot.org/core/name | "Nature"xsd:string |
| http://purl.uniprot.org/citations/12660785 | http://purl.uniprot.org/core/name | "Nature"xsd:string |