Dominant-negative effect of mutant valosin-containing protein in aggresome formation

被引：20

作者：

Kitami, MI

Kitami, T

Nagahama, M

Tagaya, M

Hori, S

Kakizuka, A

Mizuno, Y

Hattori, N

机构：

[1] Univ Tokyo, Juntendo Univ, Sch Med, Dept Neurol,Bunkyo Ku, Tokyo 1130033, Japan

[2] Juntendo Univ, Sch Med, Res Inst Dis Old Age, Tokyo 113, Japan

[3] Tokyo Univ Pharm & Life Sci, Sch Life Sci, Hachioji, Tokyo 19203, Japan

[4] Kyoto Univ, Sch Biostudies, Labs Funct Biol, Kyoto, Japan

来源：

FEBS LETTERS | 2006年 / 580卷 / 02期

关键词：

valosin-containing protein; Parkinson's disease; Lewy body; aggresome;

D O I：

10.1016/j.febslet.2005.12.044

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：

Lewy bodies (LBs) are the pathologic hallmark of Parkinson's disease. Recent studies revealed that LBs exhibit several morphologic and molecular similarities to aggresomes. Aggresomes are perinuclear aggregates representing intracellular deposits of misfolded proteins. Recently, valosin-containing protein (VCP) was one of the components of LBs, suggesting its involvement in LB formation. Here, we showed the localization of VCP in aggresomes induced by a proteasome inhibitor in cultured cells. Cells overexpressing mutant VCP (K524M: D2) showed reduced aggresome formation relative to those overexpressing wild-type and mutant (K251M:D1) VCPs. Our findings suggest that the D2 domain is involved in aggresome formation. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

引用

页码：474 / 478

页数：5

共 19 条

[1] Involvement of valosin-containing protein, an ATPase co-purified with IκBα and 26 S proteasome, in ubiquitin-proteasome-mediated degradation of IκBα [J].