Sumoylation of amyloid precursor protein negatively regulates Aβ aggregate levels

被引：97

作者：

Zhang, Yu-Qian ^{[1
]}

Sarge, Kevin D. ^{[1
]}

机构：

[1] Univ Kentucky, Dept Mol & Cellular Biochem, Lexington, KY 40536 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2008年 / 374卷 / 04期

关键词：

APP; SUMO-1; SUMO-2; ubc9; Alzheimer's;

D O I：

10.1016/j.bbrc.2008.07.109

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The proteolytic processing of amyloid precursor protein (APP) to produce A beta peptides is thought to play an important role in the mechanism of Alzheimer's disease. Here, we show that lysines 587 and 595 of APP, which are immediately adjacent to the site of beta-secretase cleavage, are covalently modified by SUMO proteins in vivo. Sumoylation of these lysine residues is associated with decreased levels of A beta aggregates. Further, overexpression of the SUMO E2 enzyme ubc9 along with SUMO-1 results in decreased levels of A beta aggregates in cells transfected with the familial Alzheimer's disease-associated V642F mutant APP, indicating the potential of up-regulating activity of the cellular sumoylation machinery as an approach against Alzheimer's disease. The results also provide the first demonstration that the SUMO E2 enzyme (ubc9) is present within the endoplasmic reticulum, indicating how APP, and perhaps other proteins that enter this compartment, can be sumoylated. (c) 2008 Elsevier Inc. All rights reserved.

引用

页码：673 / 678

页数：6

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