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

Title data

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

Official URL: Volltext

Abstract in another language

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.

Further data

Item Type: Article in a journal
Refereed: Yes
Institutions of the University: Faculties > Faculty of Engineering Science
Faculties > Faculty of Engineering Science > Chair Process Biotechnology
Faculties
Result of work at the UBT: No
DDC Subjects: 500 Science
500 Science > 500 Natural sciences
600 Technology, medicine, applied sciences
600 Technology, medicine, applied sciences > 610 Medicine and health
Date Deposited: 26 Feb 2016 11:12
Last Modified: 26 Feb 2016 11:12
URI: https://eref.uni-bayreuth.de/id/eprint/31083