Functional interactions between the estrogen receptor and DRIP205, a subunit of the heteromeric DRIP coactivator complex

Nuclear receptors regulate transcription in direct response to their cognat e hormonal ligands. Ligand binding leads to the dissociation of corepressor s and the recruitment of coactivators. Many of these factors, acting in lar ge complexes, have emerged as potential chromatin remodelers through intrin sic histone modifying activities. In addition, other ligand-recruited compl exes appear to act more directly on the transcriptional apparatus. The DRIP complex is a 15-subunit complex required for nuclear receptor transcriptio nal activation in vitro. It is recruited to the receptor in response to lig and through specific interactions of one subunit, DRIP205. Ne present evide nce that DRIP205 interacts with another member of the steroid receptor subf amily, estrogen receptor (ER). This interaction occurs in an agonist-stimul ated fashion which in turn is inhibited by several ER antagonists. In vivo, a fragment of DRIP205 containing only its receptor interacting region acts to selectively inhibit ER's ability to activate transcription in response to estradiol. These observations suggest a key role for the DRIP coactivato r complex in estrogen-ER signaling.