Cdc2 phosphorylation of nucleolin demarcates mitotic stages and Alzheimer's disease pathology

被引:74
作者
Dranovsky, A
Vincent, I
Gregori, L
Schwarzman, A
Colflesh, D
Enghild, J
Strittmatter, W
Davies, P
Goldgaber, D [1 ]
机构
[1] SUNY Stony Brook, Dept Psychiat & Behav Sci, Stony Brook, NY 11794 USA
[2] SUNY Stony Brook, Med Sci Training Program, Stony Brook, NY 11794 USA
[3] Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA
[4] SUNY Stony Brook, Microscopy Imaging Ctr, Stony Brook, NY 11794 USA
[5] Duke Univ, Dept Neurol, Durham, NC 27710 USA
关键词
nucleolin; mitosis; neurodegeneration; Alzheimer's disease;
D O I
10.1016/S0197-4580(00)00248-7
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
Nucleolin is a major multifunctional nuclear phosphoprotein that is phosphorylated by Cdc2 kinase in mitosis and that participates in a number of cellular processes. The monoclonal antibody TG-3 generated against neurofibrillary tangles (NFT) found in Alzheimer's disease (AD) is highly specific For mitotic cells: in culture. We here demonstrate that phosphorylation of nucleolin by Cdc2 kinase generates the TG-3 epitope. The unique pool of TG-3 immunoreactive nucleolin appears abruptly during the prophase. It is associated with chromosomes through the metaphase and it gradually disappears during separation of chromosomes and exit from mitosis. In the brain. nucleolin was localized not only to nuclei but also to neuronal cytoplasm, and it is a marker for early NFT. In patients with AD. Cdc2 phosphorylated nucleolin was present in NFT. These findings suggest that phosphorylation of nucleolin by Cdc2 kinase is a critical event and the point of convergence of two distinct pathways, mitosis and neurodegeneration. (C) 2001 Elsevier Science Inc. All rights reserved.
引用
收藏
页码:517 / 528
页数:12
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