Enhancement of human estrogen receptor activity by SPT6: a potential coactivator

The conserved nature of the transcriptional machinery between yeast and higher eukaryotes makes the yeast system suitable to genetically dissect the signal transduction pathway of steroid hormone receptors. This report describes the yeast protein, SPT6, which modulates the transcriptional activity of the human estrogen receptor (hER) by affecting the C-terminal activation domain. It is demonstrated that SPT6 is able to potentiate hER activity in yeast and also in mammalian cells in vivo. SPT6 interacts specifically with the hormone-binding domain of hER in vivo. The in vivo studies are substantiated by specific protein-protein interactions between SPT6 and the hormone-binding domain of hER in vitro. Therefore, the data suggest that the SPT6 protein may be involved in signal transmission of ER by acting as a coactivator.