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 exp ression and subcellular localization during neuronal development and degene ration. FAC1 localizes to the cell body and neurites in undifferentiated ne urons during development and in degenerating neurons during Alzheimer's dis ease progression. In the normal adult brain FAC1 is present predominantly i n 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 sequ ence is dramatically enhanced when FAC1 is phosphorylated. Phosphatase trea tment of neuroblastoma nuclear extracts reduces FAC1 DNA binding affinity, Finally, inhibition of cellular serine/threonine phosphatases results in in creased FAC1 DNA binding activity. These data suggest that FAC1 DNA binding activity is dependent upon and regulated by phosphorylation signals in the cell. (C) 1999 Academic Press.