Regulation of Pur alpha gene transcription: Evidence for autoregulation ofPur alpha promoter

Citation
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
Citations number
21
Categorie Soggetti
Cell & Developmental Biology
Journal title
JOURNAL OF CELLULAR PHYSIOLOGY
ISSN journal
00219541 → ACNP
Volume
186
Issue
3
Year of publication
2001
Pages
406 - 413
Database
ISI
SICI code
0021-9541(200103)186:3<406:ROPAGT>2.0.ZU;2-E
Abstract
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.