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

J A Wright, P C Mchugh, M Stockbridge, S Lane, S Kralovicova, D R Brown

Research output: Contribution to journalArticle

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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.
LanguageEnglish
Pages3809-3820
Number of pages12
JournalCellular and Molecular Life Sciences (CMLS)
Volume66
Issue number23
DOIs
StatusPublished - Dec 2009

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Introns
Inteins
Prion Diseases
Prion Proteins
Infection
Luciferases
Transcription Factors
Up-Regulation
Binding Sites

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Wright, J. A., Mchugh, P. C., Stockbridge, M., Lane, S., Kralovicova, S., & Brown, D. R. (2009). Activation and repression of prion protein expression by key regions of intron 1. DOI: 10.1007/s00018-009-0154-8

Activation and repression of prion protein expression by key regions of intron 1. / Wright, J A; Mchugh, P C; Stockbridge, M; Lane, S; Kralovicova, S; Brown, D R.

In: Cellular and Molecular Life Sciences (CMLS), Vol. 66, No. 23, 12.2009, p. 3809-3820.

Research output: Contribution to journalArticle

Wright, JA, Mchugh, PC, Stockbridge, M, Lane, S, Kralovicova, S & Brown, DR 2009, 'Activation and repression of prion protein expression by key regions of intron 1' Cellular and Molecular Life Sciences (CMLS), vol. 66, no. 23, pp. 3809-3820. DOI: 10.1007/s00018-009-0154-8
Wright JA, Mchugh PC, Stockbridge M, Lane S, Kralovicova S, Brown DR. Activation and repression of prion protein expression by key regions of intron 1. Cellular and Molecular Life Sciences (CMLS). 2009 Dec;66(23):3809-3820. Available from, DOI: 10.1007/s00018-009-0154-8
Wright, J A ; Mchugh, P C ; Stockbridge, M ; Lane, S ; Kralovicova, S ; Brown, D R. / Activation and repression of prion protein expression by key regions of intron 1. In: Cellular and Molecular Life Sciences (CMLS). 2009 ; Vol. 66, No. 23. pp. 3809-3820
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