Activation and Repression of Prion Protein Expression by Key Regions of Intron 1

Overview

Journal Cell Mol Life Sci

Publisher Springer

Specialty Biology

Date 2009 Sep 17

PMID 19756378

Citations 5

Authors

Josephine A Wright

Patrick C McHugh

Mark Stockbridge

Samantha Lane

Silvia Kralovicova

David R Brown

Affiliations

Soon will be listed here.

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.

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