A. Dranovsky et al., Cdc2 phosphorylation of nucleolin demarcates mitotic stages and Alzheimer's disease pathology, NEUROBIOL A, 22(4), 2001, pp. 517-528
Nucleolin is a major multifunctional nuclear phosphoprotein that is phospho
rylated by Cdc2 kinase in mitosis and that participates in a number of cell
ular processes. The monoclonal antibody TG-3 generated against neurofibrill
ary tangles (NFT) found in Alzheimer's disease (AD) is highly specific For
mitotic cells: in culture. We here demonstrate that phosphorylation of nucl
eolin by Cdc2 kinase generates the TG-3 epitope. The unique pool of TG-3 im
munoreactive nucleolin appears abruptly during the prophase. It is associat
ed with chromosomes through the metaphase and it gradually disappears durin
g 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 nucleoli
n by Cdc2 kinase is a critical event and the point of convergence of two di
stinct pathways, mitosis and neurodegeneration. (C) 2001 Elsevier Science I
nc. All rights reserved.