Cdc2 phosphorylation of nucleolin demarcates mitotic stages and Alzheimer's disease pathology.
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.
Dranovsky
A
A
Medical Scientist Training Program, State University of New York, Stony Brook, NY 11794, USA.
Vincent
I
I
Gregori
L
L
Schwarzman
A
A
Colflesh
D
D
Enghild
J
J
Strittmatter
W
W
Davies
P
P
Goldgaber
D
D
D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D000911:Antibodies, Monoclonal; D001921:Brain / Q000378:metabolism / Q000473:pathology; D016203:CDC2 Protein Kinase / Q000032:analysis / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms; D008938:Mitosis / Q000502:physiology; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D010750:Phosphoproteins / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D010766:Phosphorylation; D016601:RNA-Binding Proteins / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D000097796:Nucleolin
D000911:Antibodies, Monoclonal; D016203:CDC2 Protein Kinase; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D000097796:Nucleolin