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Physical interaction and functional synergy between glucocorticoid receptor and Ets2 proteins for transcription activation of the rat cytochrome P-450c27 promoter.
Mullick, J; Anandatheerthavarada, H K; Amuthan, G; Bhagwat, S V; Biswas, G; Camasamudram, V; Bhat, N K; Reddy, S E; Rao, V; Avadhani, N G.
Afiliação
  • Mullick J; Department of Animal Biology, Mari Lowe Center for Comparative Oncology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
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.
Assuntos
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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
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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