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Transcriptional activation of the human epidermal growth factor receptor promoter by human p53.
Ludes-Meyers, J H; Subler, M A; Shivakumar, C V; Munoz, R M; Jiang, P; Bigger, J E; Brown, D R; Deb, S P; Deb, S.
Afiliação
  • Ludes-Meyers JH; Department of Microbiology, University of Texas Health Science Center at San Antonio, 78284, USA.
Mol Cell Biol ; 16(11): 6009-19, 1996 Nov.
Article em En | MEDLINE | ID: mdl-8887630
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ativação Transcricional / Proteína Supressora de Tumor p53 / Regiões Promotoras Genéticas / Receptores ErbB Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Mol Cell Biol Ano de publicação: 1996 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ativação Transcricional / Proteína Supressora de Tumor p53 / Regiões Promotoras Genéticas / Receptores ErbB Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Mol Cell Biol Ano de publicação: 1996 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos