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Activation and repression of prion protein expression by key regions of intron 1

Wright, Josephine A., McHugh, Patrick C, Stockbridge, Mark, Lane, Samantha, Kralovicova, Silvia and Brown, David R. (2009) Activation and repression of prion protein expression by key regions of intron 1. Cellular and Molecular Life Sciences, 66 (23). pp. 3809-3820. ISSN 1420-682X

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Abstract

Expression of the prion protein is necessary for infection with prion diseases. Altered expression levels may play an important role in susceptibility to infection. Therefore, understanding the mechanisms that regulate prion protein expression is of great importance. It was previously shown that expression of the prion protein is to some degree regulated by an alternative promoter within intron 1. Studies using GFP and luciferase reporter systems were undertaken to determine key sites for the repression and activation of expression of the prion protein driven by intron 1. We identified a region within intron 1 sufficient to drive prion protein expression. Our findings highlight two potential repressor regions. Both regions have binding sites for the known repressor Hes-1. Hes-1 overexpression caused a dramatic decrease in PrP protein expression. Additionally, we have identified Atox-1 as a transcription factor that upregulates prion protein expression. These findings clearly indicate that intron 1 plays a key role in regulation of prion protein expression levels.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
R Medicine > RM Therapeutics. Pharmacology
Schools: School of Applied Sciences
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Depositing User: Sharon Beastall
Date Deposited: 26 Jan 2012 11:34
Last Modified: 26 Jan 2012 11:34
URI: http://eprints.hud.ac.uk/id/eprint/12651

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