含缬酪肽蛋白突变体在聚集体形成中的显性负效应。
Dominant-negative effect of mutant valosin-containing protein in aggresome formation.
作者信息
Kitami Makiko-Iijima, Kitami Toshiaki, Nagahama Masami, Tagaya Mitsuo, Hori Seiji, Kakizuka Akira, Mizuno Yoshikuni, Hattori Nobutaka
机构信息
Department of Neurology, Juntendo University School of Medicine, Bunkyo, Tokyo 113-0033, Japan.
出版信息
FEBS Lett. 2006 Jan 23;580(2):474-8. doi: 10.1016/j.febslet.2005.12.044. Epub 2005 Dec 22.
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.
路易小体（LBs）是帕金森病的病理标志。最近的研究表明，路易小体与包含体显示出几种形态学和分子上的相似性。包含体是代表错误折叠蛋白质细胞内沉积物的核周聚集体。最近，含缬酪肽蛋白（VCP）是路易小体的组成成分之一，表明其参与路易小体的形成。在此，我们展示了VCP在培养细胞中由蛋白酶体抑制剂诱导形成的包含体中的定位。与过表达野生型和突变型（K251M：D1）VCP的细胞相比，过表达突变型VCP（K524M：D2）的细胞显示出包含体形成减少。我们的研究结果表明，D2结构域参与包含体的形成。
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