| Autor: |
Li J; Department of Neurobiology, Computer Aided Drug Design, Pharmacia Corporation, Kalamazoo, Michigan 49001, USA., Pauley AM, Myers RL, Shuang R, Brashler JR, Yan R, Buhl AE, Ruble C, Gurney ME |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of neurochemistry [J Neurochem] 2002 Sep; Vol. 82 (6), pp. 1540-8. |
| DOI: |
10.1046/j.1471-4159.2002.01105.x |
| Abstrakt: |
Mutations in the human presenilin genes (PS1 or PS2) have been linked to autosomal dominant, early onset Alzheimer's disease (AD). Presenilins, probably as an essential part of gamma-secretase, modulate gamma-cleavage of the amyloid protein precursor (APP) to the amyloid beta-peptide (Abeta). Mutations in sel-12, a Caenorhabditis elegans presenilin homologue, cause a defect in egg laying that can be suppressed by loss of function mutations in a second gene, SEL-10. SEL-10 protein is a homologue of yeast Cdc4, a member of the SCF (Skp1-Cdc53/CUL1-F-box protein) E2-E3 ubiquitin ligase family. In this study, we show that human SEL-10 interacts with PS1 and enhances PS1 ubiquitination, thus altering cellular levels of unprocessed PS1 and its N- and C-terminal fragments. Co-transfection of sel-10 and APP cDNAs in HEK293 cells leads to an alteration in the metabolism of APP and to an increase in the production of amyloid beta-peptide, the principal component of amyloid plaque in Alzheimer's disease. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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