Estrogen receptor pathways to AP-1

Estrogen receptor (ER binds to estrogen response elements in target genes a nd recruits a coactivator complex of CBP-p160 that mediates stimulation of transcription. ER also activates transcription at AP-1 sites that bind the Jun/Fos transcription factors, but not ER. We review the evidence regarding mechanisms whereby ER increases the activity of Jun/Fos and propose two pa thways of ER action depending on the ER (alpha or beta) and on the ligand. We propose that estrogen-ER alpha complexes use their activation functions (AF-1 and AF-2) to bind to the p 160 component of the coactivator complex r ecruited by Jun/Fos and trigger the coactivator to a higher state of activi ty. We propose that selective estrogen receptor modulator (SERM) complexes with ER beta and with truncated ER alpha derivatives use their DNA binding domain to titrate histone deacetylase (HDAC)-repressor complexes away from the Jun/Fos coactivator complex, thereby allowing unfettered activity of th e coactivators. Finally, we consider the possible physiological significanc e of ER action at AP-1 sites. (C) 2000 Published by Elsevier Science Ltd.