RT Journal Article
SR Electronic
T1 Functional Differences between the Amino-Terminal Domains of Estrogen Receptors α and β
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 584
OP 590
DO 10.1124/mol.58.3.584
VO 58
IS 3
A1 Franck Delaunay
A1 Katarina Pettersson
A1 Michel Tujague
A1 Jan-Åke Gustafsson
YR 2000
UL http://molpharm.aspetjournals.org/content/58/3/584.abstract
AB Human estrogen receptors α (ERα) and β (ERβ) are ligand-inducible transcription factors that are highly homologous in their central DNA-binding and carboxyl-terminal ligand-binding domains. In contrast, there is very little conservation between ERα and ERβ in the amino-terminal domain. Using different human cell lines, we show that wild-type ERβ transcriptional activity is lower or similar to that of ERα, depending on the cell type. Deletion of the amino-terminal domain in both ER subtypes resulted in no or a lower decrease of transcriptional activity of ERβ compared with ERα, suggesting that the ERβ amino-terminal domain contains a weaker transcriptional activation function-1. Using ERα and ERβ deletion mutants, we showed that the amino-terminal transcriptional activity of ERβ maps to amino acids 1-31. Interestingly, this domain contains a six amino-acid motif (amino acids 5–10 in human ERβ) that is part of the ERα-activation function-1 region (amino acids 49–54 in human ERα) and highly conserved among all mammalian ERα amino-terminal domains. Despite this similarity between the two ER subtypes, no autonomous and ligand-independent activity of the ERβ-amino-terminal domain was observed in yeast and mammalian cells in contrast to ERα. This study provides a molecular basis for the difference in transcriptional activity between ERα and ERβ and establishes that ERβ contains a structurally and functionally restricted amino-terminal transcriptional activity.