Structure/Function Studies of the Androgen Receptor DNA-Binding Region
Abstract
The androgen receptor (AR) regulates the growth and differentiation of prostate cells and is an important drug target for prostate cancer chemotherapy. The research goals associated with this study are to characterize the structural and functional aspects of the AR in order to uncover the potential of its domains, and in particular the DNA-binding domain, as a drug target. In this final report, I discuss the results obtained over the past three years towards characterization of the AR. Among our findings are a) the DNA-binding domain of the androgen receptor and related nuclear receptors act as their nuclear export signals, b) their export is dependent on their binding to the protein calreticulin in the presence of calcium, c) by analogy with our recent crystal structure of EcR-Usp on DNA, a pair of DNA-binding domains are arranged symmetrically as a homodimer with respect to each other and directly on the half-sites of their target DNA, d) the ligand binding domain is analogous to the FXR ligand-binding domain and shares highly related surfaces responsible for DHT binding and coactivator binding.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2003
- Accession Number
- ADA427711
Entities
People
- Fraydoon Rastinejad
Organizations
- University of Virginia