Estrogen receptor-alpha interaction with the CREB binding protein coactivator is regulated by the cellular environment.

The p160 coactivators, steroid receptor coactivator-1 (SRC-1), transcriptional intermediary factor-2 (TIF2) and receptor-associated coactivator-3 (RAC3), as well as the coactivator/integrator CBP, mediate estrogen receptor-alpha (ERalpha)-dependent gene expression. Although these coactivators are widely expressed, ERalpha transcriptional activity is cell-type dependent. In this study, we investigated ERalpha interaction with p160 coactivators and ...
CBP in HeLa and HepG2 cell lines. Basal and estradiol (E2)-dependent interactions between the ERalpha ligand-binding domain (LBD) and SRC-1, TIF2 or RAC3 were observed in HeLa and HepG2 cells. The extents of hormone-dependent interactions were similar and interactions between each of the p160 coactivators and the ERalpha LBD were not enhanced by 4-hydroxytamoxifen in either cell type. In contrast to the situation for p160 coactivators, E2-dependent interaction of the ERalpha LBD with CBP or p300 was detected in HeLa but not HepG2 cells by mammalian two-hybrid and coimmunoprecipitation assays, indicating that the cellular environment modulates ERalpha-CBP/p300 interaction. Furthermore, interactions between CBP and p160 coactivators are much more robust in HeLa than HepG2 cells suggesting that poor CBP-p160 interactions are insufficient to support ERalpha-CBP-p160 ternary complexes important for nuclear receptor-CBP interactions. Alterations in p160 coactivators or CBP expression between these two cell types did not account for differences in ERalpha-p160-CBP interactions. Taken together, these data revealed the influence of cellular environment on ERalpha-CBP/p300 interactions, as well as CBP-p160 coactivator binding, and suggest that these differences may contribute to the cell specificity of ERalpha-dependent gene expression.
Mesh Terms:
CREB-Binding Protein, Estrogen Receptor alpha, Hela Cells, Histone Acetyltransferases, Humans, Nuclear Proteins, Nuclear Receptor Coactivator 1, Nuclear Receptor Coactivator 2, Nuclear Receptor Coactivator 3, Protein Binding, Protein Structure, Tertiary, Tamoxifen, Trans-Activators, Transcription Factors, Tumor Cells, Cultured, Two-Hybrid System Techniques
J. Mol. Endocrinol.
Date: Feb. 01, 2004
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