Par-4 Is involved in regulation of beta -secretase cleavage of the alzheimer's amyloid precursor protein

doi:10.1074/jbc.M411933200

HOME

QUICK SEARCH:

	Author:		Keyword(s):
Year:		Vol:		Page:

A more recent version of this article appeared on April 8, 2005

This Article

	Full Text (Accepted Manuscript)
	All Versions of this Article: 280/14/13824 most recent M411933200v1
	Alert me when this article is cited
	Alert me if a correction is posted

Services

	Email this article to a friend
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new issues of the journal
	Download to citation manager
	Request Permissions

Citing Articles

	Citing Articles via HighWire
	Citing Articles via Google Scholar

Google Scholar

	Articles by Xie, J.
	Articles by Guo, Q.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Xie, J.
	Articles by Guo, Q.

Social Bookmarking

	What's this?

Papers In Press, published online ahead of print January 25, 2005
J. Biol. Chem, 10.1074/jbc.M411933200
Submitted on October 20, 2004
Revised on January 25, 2005
Accepted on January 25, 2005

Par-4 Is involved in regulation of $beta$ -secretase cleavage of the alzheimer's amyloid precursor protein

Jun Xie and Qing Guo

Department of Physiology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104

Corresponding Author: qing-guo{at}ouhsc.edu

Mounting evidence indicates that aberrant production and aggregation of amyloid beta-peptide 1-42 (Abeta1-42) plays a central role in the pathogenesis of Alzheimer’s disease (AD). Abetais produced when amyloid precursor protein (APP) is cleaved by Abeta- and gamma-secretases at the N- and C-terminus of the Abeta peptide, respectively. The beta-secretase is membrane-bound aspartyl protease, most commonly known as BACE1. Since BACE1 cleaves APP at the N-terminus of the Abeta-peptide domain, it catalyzes the first step in Abeta-generation. Par-4 (Prostate apoptosis response-4) is a leucine zipper protein that was initially identified to be associated with neuronal degeneration and aberrant Abeta production in models of AD. We now report that C-terminal domain of Par-4 is necessary for forming a complex with the cytosolic tail of BACE1 in co-immunoprecipitation assays and in vitro pull-down experiments. Overexpression of Par-4 significantly increased, while silencing of Par-4 expression by RNA mediated interference (RNAi) significantly decreased, beta-secretase cleavage of APP. These results suggest that Par-4 may be directly involved in regulating the APP cleavage activity of BACE1. Since increased BACE1 activity observed in AD patients did not seem to arise from genetic mutations nor polymorphisms in BACE1, identification of Par-4 as an endogenous regulator of BACE1 activity may have significant implications for developing novel therapeutic strategies for AD.

Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

C. Lu, J.-Q. Chen, G.-P. Zhou, S.-H. Wu, Y.-F. Guan, and C.-S. Yuan
Multimolecular complex of Par-4 and E2F1 binding to Smac promoter contributes to glutamate-induced apoptosis in human- bone mesenchymal stem cells
Nucleic Acids Res., September 1, 2008; 36(15): 5021 - 5032.
[Abstract] [Full Text] [PDF]

Y. I. Yin, B. Bassit, L. Zhu, X. Yang, C. Wang, and Y.-M. Li
{gamma}-Secretase Substrate Concentration Modulates the Abeta42/Abeta40 Ratio: IMPLICATIONS FOR ALZHEIMER DISEASE
J. Biol. Chem., August 10, 2007; 282(32): 23639 - 23644.
[Abstract] [Full Text] [PDF]

J. Xie and Q. Guo
Par-4 is a novel mediator of renal tubule cell death in models of ischemia-reperfusion injury
Am J Physiol Renal Physiol, January 1, 2007; 292(1): F107 - F115.
[Abstract] [Full Text] [PDF]

J. Xie and Q. Guo
Apoptosis Antagonizing Transcription Factor Protects Renal Tubule Cells against Oxidative Damage and Apoptosis Induced by Ischemia-Reperfusion
J. Am. Soc. Nephrol., December 1, 2006; 17(12): 3336 - 3346.
[Abstract] [Full Text] [PDF]

Par-4 Is involved in regulation of -secretase cleavage of the alzheimer's amyloid precursor protein

Par-4 Is involved in regulation of $beta$ -secretase cleavage of the alzheimer's amyloid precursor protein