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PMID: 8887630 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

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

Molecular and cellular biology ·Vol. 16 ·No. 11 ·1996-11-00 ·Pages 6009-19

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

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.

MeSH Terms
Amino Acid Sequence Base Composition Base Sequence Binding Sites Chloramphenicol O-Acetyltransferase/biosynthesis ErbB Receptors/biosynthesis,genetics Humans Molecular Sequence Data Polymerase Chain Reaction Promoter Regions, Genetic Recombinant Proteins/biosynthesis Regulatory Sequences, Nucleic Acid Restriction Mapping Sequence Deletion TATA Box Transcriptional Activation Tumor Suppressor Protein p53/metabolism
Chemicals
Recombinant Proteins Tumor Suppressor Protein p53 Chloramphenicol O-Acetyltransferase ErbB Receptors
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Ludes-Meyers J H
Department of Microbiology, University of Texas Health Science Center at San Antonio, 78284, USA.
Subler M A
Shivakumar C V
Munoz R M
Jiang P
Bigger J E
Brown D R
Deb S P
Deb S
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.16.11.6009
Published
1996-11-00
Pages
6009-19
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC231603
Subset
IM
Grants
NIAID NIH HHS · AI31498-02 · United States
NCI NIH HHS · CA70712 · United States
External Links
PubMed source DOI: 10.1128/MCB.16.11.6009 PMC Full Text View journal details
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