AIB1 is a conduit for kinase-mediated growth factor signaling to the estrogen receptor

J Font de Mora, M Brown - Molecular and cellular biology, 2000 - Taylor & Francis
Molecular and cellular biology, 2000Taylor & Francis
Growth factor modulation of estrogen receptor (ER) activity plays an important role in both
normal estrogen physiology and the pathogenesis of breast cancer. Growth factors are
known to stimulate the ligand-independent activity of ER through the activation of mitogen-
activated protein kinase (MAPK) and the direct phosphorylation of ER. We found that the
transcriptional activity of AIB1, a ligand-dependent ER coactivator and a gene amplified
preferentially in ER-positive breast cancers, is enhanced by MAPK phosphorylation. We …
Growth factor modulation of estrogen receptor (ER) activity plays an important role in both normal estrogen physiology and the pathogenesis of breast cancer. Growth factors are known to stimulate the ligand-independent activity of ER through the activation of mitogen-activated protein kinase (MAPK) and the direct phosphorylation of ER. We found that the transcriptional activity of AIB1, a ligand-dependent ER coactivator and a gene amplified preferentially in ER-positive breast cancers, is enhanced by MAPK phosphorylation. We demonstrate that AIB1 is a phosphoprotein in vivo and can be phosphorylated in vitro by MAPK. Finally, we observed that MAPK activation of AIB1 stimulates the recruitment of p300 and associated histone acetyltransferase activity. These results suggest that the ability of growth factors to modulate estrogen action may be mediated through MAPK activation of the nuclear receptor coactivator AIB1.
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