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Papers In Press, published online ahead of print April 17, 2000
J. Biol. Chem, 10.1074/jbc.M002013200
Submitted on March 10, 2000
Revised on April 7, 2000
Accepted on April 17, 2000

Functional Interactions Between the Estrogen Receptor and DRIP205, a Subunit of the Heteromeric DRIP Coactivator Complex

Darya Burakov, Chi-Wai Wong, Christohpe Rachez, Boris Cheskis, and Leonard P Freedman

Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021

Corresponding Author: l-freedman{at}ski.mskcc.org

Nuclear receptors regulate transcription in direct response to their cognate hormonal ligands. Ligand-binding leads to the dissociation of corepressors and the recruitment of coactivators. Many of these factors, acting in large complexes, have emerged as potential chromatin remodelers through intrinsic histone modifying activities. In addition, other ligand-recruited complexes appear to act more directly on the transcriptional apparatus. The DRIP complex is a 15 subunit complex required for nuclear receptor transcriptional activation in vitro. It is recruited to the receptor in response to ligand through specific interactions of one subunit, DRIP205. We present evidence that DRIP205 interacts with another member of the steroid receptor subfamily, estrogen receptor (ER). This interaction occurs in an agonist-stimulated fashion which in turn is inhibited by several ER antagonists. 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 coactivator complex in estrogen-ER signalling.


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