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

Abstract:

: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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Kitami MI,Kitami T,Nagahama M,Tagaya M,Hori S,Kakizuka A,Mizuno Y,Hattori N

doi

10.1016/j.febslet.2005.12.044

keywords:

subject

Has Abstract

pub_date

2006-01-23 00:00:00

pages

474-8

issue

2

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(05)01519-X

journal_volume

580

pub_type

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