Contribution of steroid receptor coactivator-1 and CREB binding protein in ligand-independent activity of estrogen receptor beta.
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.
Tremblay
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Ste-Justine Hospital Research Center, University of Montreal, Montréal, QC, Canada H3T 1C5. atremblay@justine.umontreal.ca
Giguère
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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*
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