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Dominant‐negative effect of mutant valosin‐containing protein in aggresome formation
Author(s) -
Kitami Makiko-Iijima,
Kitami Toshiaki,
Nagahama Masami,
Tagaya Mitsuo,
Hori Seiji,
Kakizuka Akira,
Mizuno Yoshikuni,
Hattori Nobutaka
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.12.044
Subject(s) - aggresome , mutant , chemistry , biology , microbiology and biotechnology , biochemistry , gene , ubiquitin
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.