Wild-type human p53 transactivates the human proliferating cell nuclear antigen promoter.
Mol Cell Biol
; 15(12): 6785-93, 1995 Dec.
Article
em En
| MEDLINE
| ID: mdl-8524244
ABSTRACT
The wild-type p53 protein is a transcriptional activator implicated in the control of cellular growth-related gene expression. Here, using a number of different cell lines and transient-transfection-transcription assays, we demonstrate that at low levels, wild-type p53 transactivates the human proliferating cell nuclear antigen (PCNA) promoter. When expressed at a similar level, the tumor-derived p53 mutants did not transactivate the PCNA promoter. We identified a p53-binding site on the human PCNA promoter with which p53 interacts sequence specifically. When placed on a heterologous synthetic promoter, the binding site functions as a wild-type p53 response element in either orientation. Deletion of the p53-binding site renders the PCNA promoter p53 nonresponsive, showing that wild-type p53 transactivates the PCNA promoter by binding to the site. At a higher concentration, wild-type p53 inhibits the PCNA promoter but p53 mutants activate. Transactivation by p53 mutants does not require the p53-binding site. These observations suggest that moderate elevation of the cellular wild-type p53 level induces PCNA production to help in DNA repair.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ativação Transcricional
/
Proteína Supressora de Tumor p53
/
Regiões Promotoras Genéticas
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Antígeno Nuclear de Célula em Proliferação
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Mol Cell Biol
Ano de publicação:
1995
Tipo de documento:
Article
País de afiliação:
Estados Unidos