Interaction of N-terminal acetyltransferase with the cytoplasmic domain of β-amyloid precursor protein and its effect on Aβ secretion
Interaction of N-terminal acetyltransferase with the cytoplasmic domain of β-amyloid precursor protein and its effect on Aβ secretion
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DOI：
10.1093/jb/mvi014
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发表时间：
2005-02-01
影响因子：
2.7
通讯作者：
Suzuki, T
中科院分区：
文献类型：
--
作者：
Asaumi, M;Iijima, K;Suzuki, T
β-淀粉样前体蛋白（APP）的加工产生淀粉样β-蛋白（A β）并有助于阿尔茨海默病（AD）的发展。因此，阐明APP加工的调节将有助于对AD的理解。许多APP结合蛋白，如FE 65，X11 s和JNK相互作用蛋白（JIPs），都与APP胞质结构域中的681-GYENPTY-687基序结合。hARD 1表达其乙酰转移酶活性，与另一种酵母氨基乙酰转移酶hNAT 1同源的人亚基相关。细胞中hARD 1和hNAT 1的共表达抑制A β 40的分泌，并且这种抑制与其酶活性相关。这些观察结果表明，APP与hARD 1和hNAT 1和/或它们的N-乙酰转移酶活性的关联有助于调节A β的产生。
The processing of beta-amyloid precursor protein (APP) generates the amyloid beta-protein (A beta) 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. Coexpression of hARD1 and hNAT1 in cells suppressed A beta 40 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 A beta generation.