Open Access
Article
ADR1 interacts with a down-stream positive element to activate PS1 transcription
Hriday K Das1,Myrna L Baez1
1
Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX 76107, USA. hdas@hsc.unt.edu
DOI: 10.2741/2938 Volume 13 Issue 9, pp.3439-3447
Published: 01 May 2008
(This article belongs to the Special Issue Current status in alzheimers research)
Abstract

We have identified downstream promoter sequence of the PS1 gene that may be regulated by novel transcription factors. 3' deletion from +178 to +165 had no effect on PS1 transcription. 3' deletion from +178 to +140 decreased promoter activity by 50%. Further 3' deletion from +178 to +114 decreased promoter activity by 80%. Therefore, a crucial element controlling over 80% of the promoter activity in SK-N-SH cell line is located between +114 and +165. Electrophoretic mobility shift assays suggested that zinc finger proteins Sp1 and ADR1 interacted with the PS1 promoter sequence (+114 to +140) and promoter region (+140 to +165) respectively. A three base pair substitution within the core sequence (GGCGGGGA to GGCGactA) of the ADR1 consensus in the element (+140 to +165) that abolished ADR1-DNA interaction, reduced PS1 transcription by 50%. The substitution mutation in the sequence (+114 to +140) that abolished Sp1-DNA interaction had no effect on PS1 expression. These data suggest that a novel mammalian trans-activator protein ADR1 binds to the downstream element (+140 to +165) to activate PS1 transcription.

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Hriday K Das, Myrna L Baez. ADR1 interacts with a down-stream positive element to activate PS1 transcription. Frontiers in Bioscience-Landmark. 2008. 13(9); 3439-3447.