Cross-inhibition of both estrogen receptor α and β pathways by each dominant negative mutant

Both estrogen receptor alpha (ER alpha) and the recently identified ER beta are nuclear receptors that are activated by estrogen. It was reported that ER alpha and ER beta form heterodimers, Here, we show that they activate transcription independently rather than synergistically via estrogen response elements (ERE), To show the cross-talk between ER alpha and ER beta, we utilized dominant negative mutants of ERs constructed by C-terminal truncation, Interestingly, ER alpha 1-530 inhibited transactivation not only by ER alpha but also by ER beta, whereas ER beta 1-481 inhibited transactivation by ER alpha as well as by ER beta. The GST pull-down assay also demonstrated the cross-interaction of these mutants with wild-type ER alpha and ER beta. Thus, we found dominant negative mutants that block both ER alpha and ER beta signaling pathways. (C) 1998 Federation of European Biochemical Societies.