| Autor: |
Wan Ning Vanessa Chow, Jacky Chi Ki Ngo, Wen Li, Yu Wai Chen, Ka Ming Vincent Tam, Ho Yin Edwin Chan, Miller, Christopher C. J., Kwok-Fai Lau |
| Předmět: |
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| Zdroj: |
Biochemical Journal; 9/15/2015, Vol. 470 Issue 3, p303-317, 15p |
| Abstrakt: |
Alzheimer's disease (AD) is a fatal neurodegenerative disease affecting 36 million people worldwide. Genetic and biochemical research indicate that the excessive generation of amyloid- β peptide (Aβ) from amyloid precursor protein (APP), is a major part of AD pathogenesis. FE65 is a brain-enriched adaptor protein that binds to APP. However, the role of FE65 in APP processing and the mechanisms that regulate binding of FE65 to APP are not fully understood. In the present study, we show that serum- and glucocorticoid-induced kinase 1 (SGK1) phosphorylates FE65 on Ser610 and that this phosphorylation attenuates FE65 binding to APP. We also show that FE65 promotes amyloidogenic processing of APP and that FE65 Ser610 phosphorylation inhibits this effect. Furthermore, we found that the effect of FE65 Ser610 phosphorylation on APP processing is linked to a role of FE65 in metabolic turnover of APP via the proteasome. Thus FE65 influences APP degradation via the proteasome and phosphorylation of FE65 Ser610 by SGK1 regulates binding of FE65 to APP, APP turnover and processing. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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