Functional interactions between the estrogen receptor and DRIP205, a subunit of the heteromeric DRIP coactivator complex
Functional interactions between the estrogen receptor and DRIP205, a subunit of the heteromeric DRIP coactivator complex
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DOI：
10.1074/jbc.m002013200
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发表时间：
2000-07-07
影响因子：
4.8
通讯作者：
Freedman, LP
中科院分区：
文献类型：
--
作者：
Burakov, D;Wong, CW;Freedman, LP
核受体直接响应其同源激素配体调节转录。配体结合导致辅阻遏物的解离和辅激活物的募集。许多这些因素，在大的复合物中发挥作用，已经成为潜在的染色质重塑通过内在的组蛋白修饰活动。此外，其他配体募集复合物似乎更直接地作用于转录装置。DRIP复合物是体外核受体转录激活所需的15亚基复合物。它通过一个亚基DRIP 205的特异性相互作用响应配体被募集到受体。目前的证据表明，DRIP 205与类固醇受体亚家族的另一个成员，雌激素受体（ER）相互作用。这种相互作用以激动剂刺激的方式发生，反过来又被几种ER拮抗剂抑制。在体内，仅含有其受体相互作用区的DRIP 205片段可选择性抑制ER响应雌二醇激活转录的能力。这些观察结果表明，在雌激素-ER信号的DRIP辅激活复合物的关键作用。
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. Ne 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. 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 coactivator complex in estrogen-ER signaling.