Factors Modulating Estrogen Receptor Activity
Abstract
Our goal to elucidate the molecular mechanisms of transcriptional regulation by the estrogen receptor alpha (ER) in breast cancer. ER is a hormone-dependent transcription factor involved in the regulation of both normal and malignant breast cell growth by controlling target genes and signaling pathways involved in cellular proliferation. ER signal transduction and transcriptional regulation is modulated by accessory proteins and through phosphorylation. The N-terminus of ER contains a transcriptional activation function, AF-1, that is phosphorylated at four major sites in cultured mammalian cells. Several kinases have been identified that phosphorylate ER in vitro at the identified sites. Of these, we have shown that the cyclin A/ cyclin-dependent kinase 2 complex (cyclinA/Cdk2) phosphorylate serine 104 (S104) and serine 106 (S106) and that the phosphorylation of these sites is important for ER function: serine to alanine mutations of S104 and S106 decrease ER transcriptional activation. In addition, we have identified the hsp90 associated cochaperone p23 as an important regulator of the ER signaling pathway. Finally, results from our lab have established the Rho GTPases as novel modulators of ER transcriptional activation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2000
- Accession Number
- ADA385859
Entities
People
- Michael Garabedian
Organizations
- NYU Langone Health