title: Contribution of steroid receptor coactivator-1 and CREB binding protein in ligand-independent activity of estrogen receptor beta.
abstract: 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, ERalpha and ERbeta. 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 ERbeta have revealed a ligand-independent activation pathway which involves growth factor-mediated phosphorylation of ERbeta 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 ERbeta ligand-independent activation, suggesting that CBP may participate in unliganded ERbeta coactivation. These findings demonstrate the ability of alternate signaling pathways to mediate coregulator assembly, hence resulting in ligand-independent activation of ERbeta.
authors.affiliation: Ste-Justine Hospital Research Center, University of Montreal, Montréal, QC, Canada H3T 1C5. atremblay@justine.umontreal.ca
authors.forename: A
authors.initials: A
authors.lastname: Tremblay
authors.forename: V
authors.initials: V
authors.lastname: Giguère
mesh_terms: D050882:CREB-Binding Protein; D002460:Cell Line; D047629:Estrogen Receptor beta; D051548:Histone Acetyltransferases; D006801:Humans; D008024:Ligands; D009687:Nuclear Proteins / Q000378:metabolism*; D056920:Nuclear Receptor Coactivator 1; D010766:Phosphorylation; D011960:Receptors, Estrogen / Q000378:metabolism*; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D047629:Estrogen Receptor beta; D008024:Ligands; D009687:Nuclear Proteins; D011960:Receptors, Estrogen; D015534:Trans-Activators; D014157:Transcription Factors; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1