| http://purl.uniprot.org/citations/21143716 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21143716 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21143716 | http://www.w3.org/2000/01/rdf-schema#comment | "The Alzheimer's disease (AD)-associated ubiquilin-1 regulates proteasomal degradation of proteins, including presenilin (PS). PS-dependent γ-secretase generates β-amyloid (Aβ) peptides, which excessively accumulate in AD brain. Here, we have characterized the effects of naturally occurring ubiquilin-1 transcript variants (TVs) on the levels and subcellular localization of PS1 and other γ-secretase complex components and subsequent γ-secretase function in human embryonic kidney 293, human neuroblastoma SH-SY5Y and mouse primary cortical cells. Full-length ubiquilin-1 TV1 and TV3 that lacks the proteasome-interaction domain increased full-length PS1 levels as well as induced accumulation of high-molecular-weight PS1 and aggresome formation. Accumulated PS1 colocalized with TV1 or TV3 in the aggresomes. Electron microscopy indicated that aggresomes containing TV1 or TV3 were targeted to autophagosomes. TV1- and TV3-expressing cells did not accumulate other unrelated proteasome substrates, suggesting that the increase in PS1 levels was not because of a general impairment of the ubiquitin-proteasome system. Furthermore, PS1 accumulation and aggresome formation coincided with alterations in Aβ levels, particularly in cells overexpressing TV3. These effects were not related to altered γ-secretase activity or PS1 binding to TV3. Collectively, our results indicate that specific ubiquilin-1 TVs can cause PS1 accumulation and aggresome formation, which may impact AD pathogenesis or susceptibility."xsd:string |
| http://purl.uniprot.org/citations/21143716 | http://purl.org/dc/terms/identifier | "doi:10.1111/j.1600-0854.2010.01149.x"xsd:string |
| http://purl.uniprot.org/citations/21143716 | http://purl.org/dc/terms/identifier | "doi:10.1111/j.1600-0854.2010.01149.x"xsd:string |
| http://purl.uniprot.org/citations/21143716 | http://purl.uniprot.org/core/author | "Lu A."xsd:string |
| http://purl.uniprot.org/citations/21143716 | http://purl.uniprot.org/core/author | "Lu A."xsd:string |
| http://purl.uniprot.org/citations/21143716 | http://purl.uniprot.org/core/author | "Thomas A."xsd:string |
| http://purl.uniprot.org/citations/21143716 | http://purl.uniprot.org/core/author | "Thomas A."xsd:string |
| http://purl.uniprot.org/citations/21143716 | http://purl.uniprot.org/core/author | "Hyman B.T."xsd:string |
| http://purl.uniprot.org/citations/21143716 | http://purl.uniprot.org/core/author | "Hyman B.T."xsd:string |
| http://purl.uniprot.org/citations/21143716 | http://purl.uniprot.org/core/author | "Tanzi R.E."xsd:string |
| http://purl.uniprot.org/citations/21143716 | http://purl.uniprot.org/core/author | "Tanzi R.E."xsd:string |
| http://purl.uniprot.org/citations/21143716 | http://purl.uniprot.org/core/author | "Bottcher C."xsd:string |
| http://purl.uniprot.org/citations/21143716 | http://purl.uniprot.org/core/author | "Bottcher C."xsd:string |
| http://purl.uniprot.org/citations/21143716 | http://purl.uniprot.org/core/author | "Hiltunen M."xsd:string |
| http://purl.uniprot.org/citations/21143716 | http://purl.uniprot.org/core/author | "Hiltunen M."xsd:string |
| http://purl.uniprot.org/citations/21143716 | http://purl.uniprot.org/core/author | "Miettinen R."xsd:string |
| http://purl.uniprot.org/citations/21143716 | http://purl.uniprot.org/core/author | "Miettinen R."xsd:string |
| http://purl.uniprot.org/citations/21143716 | http://purl.uniprot.org/core/author | "Soininen H."xsd:string |
| http://purl.uniprot.org/citations/21143716 | http://purl.uniprot.org/core/author | "Soininen H."xsd:string |
| http://purl.uniprot.org/citations/21143716 | http://purl.uniprot.org/core/author | "Romano D."xsd:string |
| http://purl.uniprot.org/citations/21143716 | http://purl.uniprot.org/core/author | "Romano D."xsd:string |
| http://purl.uniprot.org/citations/21143716 | http://purl.uniprot.org/core/author | "Haapasalo A."xsd:string |
| http://purl.uniprot.org/citations/21143716 | http://purl.uniprot.org/core/author | "Haapasalo A."xsd:string |