p300 is a component of an estrogen receptor coactivator complex.
The estrogen receptor (ER) is a ligand-dependent transcription factor that regulates expression of target genes in response to estrogen in concert with other cellular signaling pathways. This suggests that the mechanism by which ER transmits an activating signal to the general transcription machinery may include factors that integrate these diverse signals. We have previously characterized the estrogen receptor-associated protein, ERAP160, as a factor that complexes with ER in an agonist-dependent manner. We have now found that the transcriptional coactivator p300 associates with agonist bound ER and augments ligand-dependent activation by ER. Our studies show that an ER coactivator complex involves a direct hormone-dependent interaction between ER and ERAP160, resulting in the recruitment of p300. In addition, antibodies directed against the cloned steroid receptor coactivator 1 (SRC1) recognize ERAP160. The known role of p300 in multiple signal transduction pathways, including those involving the second messenger cAMP, suggests p300 functions as a point of integration between ER and these other pathways.
Hanstein
B
B
Division of Neoplastic Disease Mechanisms, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Eckner
R
R
DiRenzo
J
J
Halachmi
S
S
Liu
H
H
Searcy
B
B
Kurokawa
R
R
Brown
M
M
D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms; D002460:Cell Line; D002522:Chlorocebus aethiops; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005982:Glutathione Transferase / Q000096:biosynthesis; D051548:Histone Acetyltransferases; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D056920:Nuclear Receptor Coactivator 1; D056918:Nuclear Receptor Coactivators; D014176:Protein Biosynthesis; D011506:Proteins / Q000302:isolation & purification / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators; D014157:Transcription Factors / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; C455500:NCOA7 protein, human; D009687:Nuclear Proteins; D056918:Nuclear Receptor Coactivators; D011506:Proteins; D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1; D005982:Glutathione Transferase