文章基本信息

标题：JNK-interacting protein-1 promotes transcription of Aβ protein precursor but not Aβ precursor-like proteins, mechanistically different than Fe65
本地全文：下载
作者：Meir H. Scheinfeld ; Shuji Matsuda ; Luciano D'Adamio 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：4
页码：1729-1734
DOI：10.1073/pnas.0437908100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Processing of the amyloid {beta} protein precursor (A{beta}PP) by the {beta} and {gamma} secretases leads to the production of two small peptides, amyloid {beta} and the A{beta}PP intracellular domain (AID, or called elsewhere AICD). Whereas the role of amyloid {beta} in the pathogenesis of Alzheimer's disease has been studied extensively, only recently has information begun to accumulate as to the role of AID. Functions identified for AID include its ability to trigger apoptosis and a role in regulating gene transcription, particularly in combination with the A{beta}PP binding protein Fe65. Here, we report that AID in combination with Janus kinase interacting protein-1 (JIP-1) can activate gene expression. We demonstrate that the mechanism is different from activation in combination with Fe65 by first showing that although Fe65 enters the nucleus in the absence of full-length A{beta}PP, JIP-1 does not. Additionally, JIP-1-induced activation is Tip60 independent, whereas a complex with AID, Fe65, and Tip60 is formed for Fe65-induced activation. Finally, and probably most interestingly, we show that although the A{beta}PP family members APLP1 and APLP2 (for amyloid {beta} precursor-like protein) can cause activation in combination with Fe65, APLP1 and APLP2 show little or no activation in combination with JIP-1. This activity for the AID fragment may help explain the unique functions of A{beta}PP relative to its other family members, and changes in gene expression found in Alzheimer's disease.