P300 is a Component of an Estrogen Receptor Coactivator Complex
Overview
Affiliations
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.
Serine starvation silences estrogen receptor signaling through histone hypoacetylation.
Li A, He B, Karagiannis D, Li Y, Jiang H, Srinivasan P Proc Natl Acad Sci U S A. 2023; 120(38):e2302489120.
PMID: 37695911 PMC: 10515173. DOI: 10.1073/pnas.2302489120.
Rekawiecki R, Wrobel M, Zajac P, Serej O, Kowalik M Animals (Basel). 2023; 13(17).
PMID: 37685048 PMC: 10486568. DOI: 10.3390/ani13172784.
Balcazar Lopez C, Albrecht J, Hafstad V, Borjesson Freitag C, Vallon-Christersson J, Bellodi C Cancer Med. 2023; 12(18):18931-18945.
PMID: 37676103 PMC: 10557849. DOI: 10.1002/cam4.6508.
ESR1 fusions and therapeutic resistance in metastatic breast cancer.
Nagy Z, Jeselsohn R Front Oncol. 2023; 12:1037531.
PMID: 36686845 PMC: 9848494. DOI: 10.3389/fonc.2022.1037531.
Yang H, Xue M, Su P, Zhou Y, Li X, Li Z J Exp Clin Cancer Res. 2022; 41(1):364.
PMID: 36581998 PMC: 9801641. DOI: 10.1186/s13046-022-02576-y.