Transcriptional activation of the human epidermal growth factor receptor promoter by human p53.

Abstract:

:The human epidermal growth factor receptor (EGFR) promoter is activated by both wild-type and tumor-derived mutant p53. In this communication, we demonstrate that EGFR promoter sequence requirements for transactivation by wild-type and mutant p53 are different. Transient-expression assays with EGFR promoter deletions identified a wild-type human p53 response element, 5'-AGCTAGACGTCCGGGCAGCCCCCGGCG -3', from positions --265 to --239. Electrophoretic mobility shift analysis and DNase I footprinting assays indicated that wild-type p53 binds sequence specifically to the response element. Using circularly permuted DNA fragments containing the p53-binding site, we show that wild-type p53 binding induces 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-type p53-binding site is transactivated by the p53 mutants but not by the wild-type protein, showing a difference in the mechanism of transactivation by wild-type and mutant p53. Transactivation of the EGFR promoter by p53 may represent a novel mechanism of cell growth regulation.

journal_name

Mol Cell Biol

authors

Ludes-Meyers JH,Subler MA,Shivakumar CV,Munoz RM,Jiang P,Bigger JE,Brown DR,Deb SP,Deb S

doi

10.1128/mcb.16.11.6009

subject

Has Abstract

pub_date

1996-11-01 00:00:00

pages

6009-19

issue

11

eissn

0270-7306

issn

1098-5549

journal_volume

16

pub_type

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