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

被引:12
作者
Jordan-Sciutto, KL [1 ]
Dragich, JM [1 ]
Bowser, R [1 ]
机构
[1] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15261 USA
关键词
Alzheimer's disease; transcription factor; DNA binding; gene regulation; phosphorylation;
D O I
10.1006/bbrc.1999.0986
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (C) 1999 Academic Press.
引用
收藏
页码:785 / 789
页数:5
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