V. Muralidharan et al., Regulation of Pur alpha gene transcription: Evidence for autoregulation ofPur alpha promoter, J CELL PHYS, 186(3), 2001, pp. 406-413
The single-stranded DNA and RNA binding protein, Pur alpha, has recently re
ceived special attention as this protein, by associating with the specific
nucleotide sequence (GGN repeats) and/or several important cellular and vir
al proteins regulates crucial biological events such as transcription, repl
ication, and cell proliferation. In this study, we focused on the promoter
activity of the Pur alpha upstream DNA sequence and demonstrated that the s
equence spanning 6,000 nucleotides upstream of the Pur alpha transcription
start site has promoter activity in various cell types. Results from promot
er deletion studies revealed that this region encompasses various regulator
y motifs which differentially participate in the promoter activity of Pur a
lpha in various cells. The transcription start site of Pur alpha is surroun
ded by the GA/GC-rich sequence which exhibits the ability to interact with
Pur alpha, suggesting a role for autoregulation of Pur alpha transcription.
Results from cotransfection studies revealed that ectopic expression of Pu
r alpha reduced transcriptional activity of the Pur alpha. promoter and the
region located between amino acid residues, 1-85 of Pur alpha is important
for the observed autoregulatory event. The regulatory protein of the human
neurotropic virus, ICV, T-antigen, which interacts with Pur alpha, decreas
ed transcriptional activity of the Pur alpha promoter. Co-expression of JCV
T-antigen and Pur alpha had no significant effect on the suppression of Pu
r alpha gene transcription by either protein. The importance of this findin
g in light of earlier results showing down regulation of Pur alpha during I
CV infection of glial cells is discussed. (C) 2001 Wiley-Liss, Inc.