Transactivation Function-2 of Estrogen Receptor α Contains Transactivation Function-1-regulating Element.

摘要: ERα has a ligand-dependent transactivation function in the ligand binding domain of C terminus (AF-2) and ligand-independent activation N (AF-1). It is still not fully understood how AF-1 AF-2 activities are regulated cooperatively by ligands. To evaluate involvement estrogenic various compounds, we analyzed these functions using AF-1-truncated AF-2-mutated mutants. composed two domains with flexible static regions. We used an region mutant mutant. Both mutants have been reported as non-E2 responsive due to disruption E2-mediated coactivator recruitment AF-2. The were activated agonists, but surprisingly antagonists selective estrogen receptor modulators (SERMs) This antagonist reversal activity was derived from AF-1. Furthermore, demonstrated that contains suppression C-terminal-truncated From findings hypothesized mutation disrupted its ability suppress AF-1, causing reversal. assess AF-2-mediated suppression, transcription physically separated novel hybrid reporter assay. observed suppressed SERMs did induce AF-1-mediated AF-2, which differed intact protein. These results imply SERM dependent on conformational change full-length molecule, allows for activation. Background: mechanism mediated N-terminal (AF-1) regulation unclear. Results: Disruption C-terminal resulted AF-1-dependent agonists. Conclusions: repression activity. Significance: may explain partial agonist/antagonist selected modulators.