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A dual specificity promoter system combining cell cycle-regulated and tissue-specific transcriptional control

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Nettelbeck, Dirk M. ; Jérôme, Valérie ; Müller, Rolf:
A dual specificity promoter system combining cell cycle-regulated and tissue-specific transcriptional control.
In: Gene Therapy. Bd. 6 (1999) Heft 7 . - S. 1276-1281.
ISSN 1476-5462

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Link zum Volltext (externe URL): Volltext

Abstract

The expression of both proliferation-associated and cell type-specific genes is a hallmark of both cancer cells and tumor endothelial cells. The possibility to combine both features in a single transcriptional control unit would greatly increase the selectivity of vectors used for cancer gene therapy. Previous studies by our laboratory have shown that the transcription of several cell cycle genes is regulated by a novel cell cycle-regulated repressor, termed CDF-1. This repressor functions by blocking in resting cells the transcriptional activation by specific factors binding to the upstream activating sequence (UAS), most notably the CCAAT-box binding factor NF-Y/CBF. Based on this work we have developed a dual specificity promoter system that combines cell type specificity with cell cycle regulation. A chimeric transcription factor (Gal4/NF-Y) consisting of the transactivation domain of NF-Y and the DNA-binding domain of Gal4 is expressed from a tissue-specific promoter. Gal4/NF-Y can bind to a second promoter consisting of a minimal cyclin A promoter with multiple Gal4 binding sites replacing the normal UAS. This leads to the tissue-specific expression of Gal4/NF-Y whose stimulatory activity on the promoter is restrained in resting cells by the recruitment of the CDF-1 repressor to the promoter. The functionality of this system is demonstrated for the specific transcriptional targeting of proliferating melanoma cells, where cell cycle regulation was >20-fold and cell type specificity was >50-fold.

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Publikationsform: Artikel in einer Zeitschrift
Begutachteter Beitrag: Ja
Institutionen der Universität: Fakultäten > Fakultät für Ingenieurwissenschaften
Fakultäten > Fakultät für Ingenieurwissenschaften > Lehrstuhl Bioprozesstechnik
Fakultäten
Titel an der UBT entstanden: Nein
Themengebiete aus DDC: 500 Naturwissenschaften und Mathematik
500 Naturwissenschaften und Mathematik > 500 Naturwissenschaften
600 Technik, Medizin, angewandte Wissenschaften
600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
Eingestellt am: 26 Feb 2016 11:12
Letzte Änderung: 26 Feb 2016 11:12
URI: https://eref.uni-bayreuth.de/id/eprint/31083