Interaction of N-terminal acetyltransferase with the cytoplasmic domain of beta-amyloid precursor protein and its effect on A beta secretion.
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. Co-expression of hARD1 and hNAT1 in cells suppressed A beta40 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.
Asaumi
Makoto
M
Laboratory of Neurobiophysics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033.
Iijima
Koichi
K
Sumioka
Akio
A
Iijima-Ando
Kanae
K
Kirino
Yutaka
Y
Nakaya
Tadashi
T
Suzuki
Toshiharu
T
D000123:Acetyltransferases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D001191:Arylamine N-Acetyltransferase / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D020798:Two-Hybrid System Techniques
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D007527:Isoenzymes; D000123:Acetyltransferases; C061313:protein N-terminal acetyltransferase; D001191:Arylamine N-Acetyltransferase; C089384:N-acetyltransferase 1