DNA binding activity of the fetal Alz-50 clone 1 (FAC1) protein is enhanced by phosphorylation

Biochem Biophys Res Commun. 1999 Jul 14;260(3):785-9. doi: 10.1006/bbrc.1999.0986.

Abstract

Fetal Alz-50 clone 1 (FAC1) is a novel DNA binding protein with altered expression and subcellular localization during neuronal development and degeneration. FAC1 localizes to the cell body and neurites in undifferentiated neurons during development and in degenerating neurons during Alzheimer's disease progression. In the normal adult brain FAC1 is present predominantly in the nucleus of cortical neurons. When in the nucleus FAC1 has been shown to repress transcription by binding a specific DNA sequence. In the present study we demonstrate that the affinity of FAC1 for the identified DNA sequence is dramatically enhanced when FAC1 is phosphorylated. Phosphatase treatment of neuroblastoma nuclear extracts reduces FAC1 DNA binding affinity. Finally, inhibition of cellular serine/threonine phosphatases results in increased FAC1 DNA binding activity. These data suggest that FAC1 DNA binding activity is dependent upon and regulated by phosphorylation signals in the cell.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acid Phosphatase / metabolism
  • Adenosine Triphosphate / metabolism
  • Animals
  • Antigens, Nuclear
  • Cell Nucleus / metabolism
  • DNA / genetics
  • DNA / metabolism*
  • DNA-Binding Proteins / isolation & purification
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Nerve Tissue Proteins / isolation & purification
  • Nerve Tissue Proteins / metabolism*
  • Neuroblastoma
  • Neurons / metabolism*
  • Nuclear Proteins / metabolism
  • Okadaic Acid / pharmacology
  • PC12 Cells
  • Phosphoprotein Phosphatases / antagonists & inhibitors
  • Phosphoprotein Phosphatases / metabolism
  • Phosphorylation
  • Protein Binding
  • Rats
  • Recombinant Fusion Proteins / isolation & purification
  • Recombinant Fusion Proteins / metabolism
  • Response Elements / genetics
  • Transcription Factors*
  • Tumor Cells, Cultured

Substances

  • Antigens, Nuclear
  • DNA-Binding Proteins
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Recombinant Fusion Proteins
  • Transcription Factors
  • fetal Alzheimer antigen
  • Okadaic Acid
  • Adenosine Triphosphate
  • DNA
  • Phosphoprotein Phosphatases
  • Acid Phosphatase