Identification of a novel aspartic protease (Asp 2) as β-secretase
Identification of a novel aspartic protease (Asp 2) as β-secretase
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DOI：
10.1006/mcne.1999.0811
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发表时间：
1999-12-01
影响因子：
3.5
通讯作者：
Christie, G
中科院分区：
文献类型：
--
作者：
Hussain, I;Powell, D;Christie, G
阿尔茨海默病β-淀粉样肽（Ap）是通过β-和γ-分泌酶的顺序作用从1型整合膜糖蛋白淀粉样前体蛋白（APP）切除而产生的。在这里，我们报告，Asp 2，一种新的跨膜天冬氨酸蛋白酶，具有预期的β-分泌酶的关键活动。在表达APP的细胞中，Asp 2的瞬时表达导致APP的N-末端片段的分泌增加和细胞相关的C-末端β-分泌酶APP片段的分泌增加。Asp 2中任一个推定的催化性乙酰基残基的突变消除了在β-分泌酶位点处裂解的片段特征的产生。这种酶存在于正常和阿尔茨海默病（AD）的大脑中，也存在于已知产生A β的细胞系中。Asp 2定位于转染细胞中的高尔基体/内质网，并在稳定表达APP的751-氨基酸同种型的细胞中显示出与APP的明确共定位。
The Alzheimer's disease beta-amyloid peptide (Ap) is produced by excision from the type 1 integral membrane glycoprotein amyloid precursor protein (APP) by the sequential actions of beta- and then gamma-secretases. Here we report that Asp 2, a novel transmembrane aspartic protease, has the key activities expected of beta-secretase. Transient expression of Asp 2 in cells expressing APP causes an increase in the secretion of the N-terminal fragment of APP and an increase in the cell-associated C-terminal beta-secretase APP fragment. Mutation of either of the putative catalytic aspartyl residues in Asp 2 abrogates the production of the fragments characteristic of cleavage at the beta-secretase site. The enzyme is present in normal and Alzheimer's disease (AD) brain and is also found in cell lines known to produce A beta. Asp 2 localizes to the Golgi/endoplasmic reticulum in transfected cells and shows clear colocalization with APP in cells stably expressing the 751-amino-acid isoform of APP.