Physical interaction and functional synergy between glucocorticoid receptor and Ets2 proteins for transcription activation of the rat cytochrome P-450c27 promoter.
J Biol Chem
; 276(21): 18007-17, 2001 May 25.
Article
em En
| MEDLINE
| ID: mdl-11279115
We demonstrate that dexamethasone-mediated transcription activation of the cytochrome P-450c27 promoter involves a physical interaction and functional synergy between glucocorticoid receptor (GR) and Ets2 factor. Ets2 protein binding to a "weak" Ets-like site of the promoter is dependent on GR bound to the adjacent cryptic glucocorticoid response element. Coimmunoprecipitation and chemical cross-linking experiments show physical interaction between GR and Ets2 proteins. Mutational analyses show synergistic effects of Ets2 and GR in dexamethasone-mediated activation of the cytochrome P-450c27 promoter. The DNA-binding domain of GR, lacking the transcription activation and ligand-binding domains, was fully active in synergistic activation of the promoter with intact Ets2. The DNA-binding domain of Ets2 lacking the transcription activation domain showed a dominant negative effect on the transcription activity. Finally, a fusion protein consisting of the GR DNA-binding domain and the transcription activation domain of Ets2 fully supported the transcription activity, suggesting a novel synergy between the two proteins, which does not require the transactivation domain of GR. Our results also provide new insights on the role of putative weak consensus Ets sites in transcription activation, possibly through synergistic interaction with other gene-specific transcription activators.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
/
Esteroide Hidroxilases
/
Fatores de Transcrição
/
Receptores de Glucocorticoides
/
Ativação Transcricional
/
Transativadores
/
Proteínas Proto-Oncogênicas
/
Sistema Enzimático do Citocromo P-450
/
Proteínas de Ligação a DNA
Limite:
Animals
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Estados Unidos
País de publicação:
Estados Unidos