TRANSCRIPTIONAL ACTIVATION OF THE HUMAN EPIDERMAL GROWTH-FACTOR RECEPTOR PROMOTER BY HUMAN P53

Citation
Jh. Ludesmeyers et al., TRANSCRIPTIONAL ACTIVATION OF THE HUMAN EPIDERMAL GROWTH-FACTOR RECEPTOR PROMOTER BY HUMAN P53, Molecular and cellular biology, 16(11), 1996, pp. 6009-6019
Citations number
123
Categorie Soggetti
Biology,"Cell Biology
ISSN journal
02707306
Volume
16
Issue
11
Year of publication
1996
Pages
6009 - 6019
Database
ISI
SICI code
0270-7306(1996)16:11<6009:TAOTHE>2.0.ZU;2-T
Abstract
The human epidermal growth factor receptor (EGFR) promoter is activate d by both wild-type and tumor-derived mutant p53. In this communicatio n, we demonstrate that EGFR promoter sequence requirements for transac tivation by wild-type and mutant p53 are different. Transient-expressi on assays with EGFR promoter deletions identified a wild-type human p5 3 response element, 5'-AGCTAGACGTCCGGGCAGCCCCCGGCG -3', from positions -265 to -239. Electrophoretic mobility shift analysis and DNase I foo tprinting assays indicated that wild-type p53 binds sequence specifica lly to the response element. Using circularly permuted DNA fragments c ontaining the p53-binding site, we show that wild-type p53 binding ind uces DNA bending at this site. We further show that the EGFR promoter is also activated by tumor-derived p53 mutants p53-143A, p53-175H, p53 -248W, p53-273H, and p53-281G. However, the transactivation by mutant p53 does not require the wild-type p53-binding site. The minimal EGFR promoter from positions -104 to -20 which does not contain the wild-ty pe p53-binding site is transactivated by the p53 mutants but not by th e wild-type protein, showing a difference in the mechanism of transact ivation by wild-type and mutant p53. Transactivation of the EGFR promo ter by p53 may represent a novel mechanism of cell growth regulation.