Function of Estrogen Receptor Tryosine Phosphorylation
Abstract
The human estrogen receptor (hER), is the in vivo target of the female sex hormone estrogen. It is also the therapeutic target of various antiestrogens used during hormonal treatment in the battle of breast cancer. Many aspects of the hER function are regulated by phosphorylation. This includes transcriptional activity, DNA binding affinity and dimerization. This research project is investigating the role of tyrosine phosphorylation on the dimerization of the hER. It has been demonstrated in vitro that a 12 amino acid phosphotyrosyl peptide can prevent dimerization of the ER, acting as a pure antiestrogen. We have identified a region within the hER capable of binding a phosphotyrosyl peptide. The specificity of this interaction was further investigated using seven amino acid phosphotyrosyl peptides where it was found that the residues C-terminal to the Y537 (i.e., 536 to 542) are necessary and sufficient for blocking hER dimerization. Individual residues within this carboxy terminal region are more importance than others. These peptides represent a potentially new class of antiestrogens which appear to function with a completely different mechanism than the classical steroidal antiestrogens.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1997
- Accession Number
- ADB228950
Entities
People
- Matthew R. Yudt
Organizations
- University of Rochester