Characterization of the Amino-terminal Transcriptional Activation Function of the Human Estrogen Receptor in Animal and Yeast Cellsстатья из журнала
Аннотация: 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. 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.
Год издания: 1995
Авторы: Daniel Metzger, Simak Ali, Jean‐Marc Bornert, Pierre Chambon
Издательство: Elsevier BV
Источник: Journal of Biological Chemistry
Ключевые слова: Estrogen and related hormone effects, Genomics, phytochemicals, and oxidative stress, Bioactive Compounds and Antitumor Agents
Другие ссылки: Journal of Biological Chemistry (PDF)
Journal of Biological Chemistry (HTML)
HAL (Le Centre pour la Communication Scientifique Directe) (HTML)
PubMed (HTML)
Journal of Biological Chemistry (HTML)
HAL (Le Centre pour la Communication Scientifique Directe) (HTML)
PubMed (HTML)
Открытый доступ: hybrid
Том: 270
Выпуск: 16
Страницы: 9535–9542