Cross-inhibition of both estrogen receptor alpha and beta pathways by each dominant negative mutant

Both estrogen receptor alpha (ERalpha) and the recently identified ERbeta are nuclear receptors that are activated by estrogen. It was reported that ERalpha and ERbeta form heterodimers. Here, we show that they activate transcription independently rather than synergistically via estrogen response elements (ERE). To show the cross-talk between ERalpha and ERbeta, we utilized dominant negative mutants of ERs constructed by C-terminal truncation. Interestingly, ERalpha1-530 inhibited transactivation not only by ERalpha but also by ERbeta, whereas ERbeta1-481 inhibited transactivation by ERalpha as well as by ERbeta. The GST pull-down assay also demonstrated the cross-interaction of these mutants with wild-type ERalpha and ERbeta. Thus, we found dominant negative mutants that block both ERalpha and ERbeta signaling pathways.