Characterization of the amino-terminal transcriptional activation function of the human estrogen receptor in animal and yeast cells.
Fiche publication
Date publication
avril 1995
Journal
The Journal of biological chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CHAMBON Pierre, Dr METZGER Daniel
Tous les auteurs :
Metzger D, Ali S, Bornert JM, Chambon P
Lien Pubmed
Résumé
We have previously reported that the transcriptional activation function AF-1, located in the A/B region of the human estrogen receptor, exhibits cell-type and promoter context specificity in both animal cells and yeast. To further characterize AF-1, we have constructed a number of deletion mutants spanning the A/B region in the context of either the whole human estrogen receptor or the A/B region linked to the GAL4 DNA binding domain, and tested their transcriptional activity in chicken embryo fibroblasts and in yeast cells, two cell types in which AF-1 efficiently activates transcription on its own. Additionally, we utilized HeLa cells in which AF-1 is poorly active but can synergize with the transcriptional activation function AF-2 located in the hormone binding domain. We show that in animal cells the "independent" activity of AF-1 is embodied in a rather hydrophobic proline-rich 99-amino acid activating domain (amino acids 51-149), whereas amino acids 51-93 and 102-149 can independently synergize with AF-2. Interestingly, in yeast, three discrete activating domains (amino acids 1-62, 80-113, and 118-149) are almost as active on their own as the whole A/B region, indicating that multiple activating domains can operate independently in yeast. Our study also demonstrates that, within the context of the whole human estrogen receptor, the same AF-1 activating domains are "induced" by either estradiol or 4-hydroxytamoxifen.
Mots clés
Animals, Base Sequence, Chick Embryo, Estradiol, pharmacology, HeLa Cells, Humans, Molecular Sequence Data, Receptors, Estrogen, chemistry, Tamoxifen, analogs & derivatives, Transcriptional Activation, Yeasts
Référence
J. Biol. Chem.. 1995 Apr;270(16):9535-42