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

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.