Contribution of steroid receptor coactivator-1 and CREB binding protein in ligand-independent activity of estrogen receptor β

Estrogens are essential regulators in the development and control of reproductive functions. The estrogenic signal is now known to be transduced by two estrogen receptors, ER and ER beta. Hormone-dependent transcriptional activation of ER and other nuclear receptors involves assembly of a coactivation complex which includes various cofactors such as the steroid receptor-coactivators (SRC) and CREB binding protein (CBP). Our findings on ER beta have revealed a ligand-independent activation pathway which involves growth factor-mediated phosphorylation of ER beta activation function-1 (AF-1) and subsequent recruitment of SRC-1 independently of the presence of estrogens. The presence of the cointegrator CBP is also shown to potentiate the SRC-1-mediated ER beta ligand-independent activation, suggesting that CBP may participate in unliganded ER beta coactivation. These findings demonstrate the ability of alternate signaling pathways to mediate coregulator assembly, hence resulting in ligand-independent activation of ER beta. (C) 2001 Elsevier Science Ltd. All rights reserved.