DNA binding activity of the fetal Alz-50 clone 1 (FAC1) protein is enhanced by phosphorylation.
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.
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, 15261, USA.
K L
KL
Jordan-Sciutto
J M
JM
Dragich
R
R
Bowser
D000135:Acid Phosphatase / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D034961:Antigens, Nuclear; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000302:isolation & purification / Q000378:metabolism*; D009447:Neuroblastoma; D009474:Neurons / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D019319:Okadaic Acid / Q000494:pharmacology; D016716:PC12 Cells; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D000092468:Bromodomain Containing Proteins
D000135:Acid Phosphatase; D000255:Adenosine Triphosphate; D034961:Antigens, Nuclear; D004247:DNA; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C406238:fetal Alzheimer antigen; D000092468:Bromodomain Containing Proteins