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

Neurobiol Aging. Jul-Aug 2001;22(4):517-28. doi: 10.1016/s0197-4580(00)00248-7.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology*
  • Antibodies, Monoclonal
  • Brain / metabolism
  • Brain / pathology
  • CDC2 Protein Kinase / analysis
  • CDC2 Protein Kinase / metabolism*
  • Carcinoma, Hepatocellular
  • Cytoplasm / chemistry
  • Cytoplasm / metabolism
  • Humans
  • Liver Neoplasms
  • Mitosis / physiology
  • Nerve Degeneration / metabolism
  • Nerve Degeneration / pathology
  • Neurofibrillary Tangles / metabolism
  • Neurofibrillary Tangles / pathology
  • Phosphoproteins / analysis
  • Phosphoproteins / immunology
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • RNA-Binding Proteins / analysis
  • RNA-Binding Proteins / immunology
  • RNA-Binding Proteins / metabolism*
  • Tumor Cells, Cultured


  • Antibodies, Monoclonal
  • Phosphoproteins
  • RNA-Binding Proteins
  • nucleolin
  • CDC2 Protein Kinase