Inhibition of Estrogen Receptor Action by the Orphan Receptors, SHP and DAX-1
Abstract
The estrogen receptor (ER) is a critical diagnostic marker and therapeutic target for a large number of breast cancers. The elucidation of the mechanisms by which ER controls the growth of certain breast cancers may provide new targets of intervention that would disrupt estrogen signaling in hormone-dependent breast cancers. SHP and Dax-1 are members of the nuclear receptor superfamily of ligand activated transcription factors that have been shown to interact with other nuclear receptors in a hormone dependent manner. In support of grant number DAMD17-99-1-9163 the findings presented here describe interactions between ER and DAX-1 and also ER and SHP. These interactions have been determined to be both direct and hormone-dependent. Functional studies of this interaction indicate that both DAX-1 and SHP act as negative regulators of ER signaling. Mutational analysis has identified regions in the amino-terminus of SHP and DAX-1 that are required for the interaction with ER. These analyses have demonstrated that subtle variations of a leucine-rich motif LXXLL, found within SHP and DAX-1 mediate the interaction. These studies suggest that SHP and DAX may act as negative regulators of ER signaling that may compete with the p160 coactivators and help to recruit co-repressors.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2001
- Accession Number
- ADA403608
Entities
People
- James Direnzo
Organizations
- Dana–Farber Cancer Institute