Interaction of N-Terminal Acetyltransferase with the Cytoplasmic Domain of -Amyloid Precursor Protein and Its Effect on A Secretion
- 1 February 2005
- journal article
- research article
- Published by Oxford University Press (OUP) in The Journal of Biochemistry
- Vol. 137 (2) , 147-155
- https://doi.org/10.1093/jb/mvi014
Abstract
The processing of β-amyloid precursor protein (APP) generates the amyloid β-protein (Aβ) and contributes to the development of Alzheimer’s disease (AD). Elucidating the regulation of APP processing will, therefore, contribute to the understanding of AD. Many APP-binding proteins, such as FE65, X11s, and JNK-interacting proteins (JIPs), bind the motif 681-GYENPTY-687 within the cytoplasmic domain of APP. Here we found that the human homologue of yeast amino-terminal acetyltransferase ARD1 (hARD1) interacts with a novel motif, 658-HGVVEVD-664, in the cytoplasmic domain of APP695. hARD1 expressed its acetyltransferase activity in association with a human subunit homologous to another yeast amino-acetyltransferase, hNAT1. Co-expression of hARD1 and hNAT1 in cells suppressed Aβ40 secretion and the suppression correlated with their enzyme activity. These observations suggest that the association of APP with hARD1 and hNAT1 and/or their N-acetyltransferase activity contributes to the regulation of Aβ generation.Keywords
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