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Functional Motifs of the Androgen Receptor

  • Elizabeth M. Wilson
Chapter

Abstract

Androgen receptor (AR) transcriptional activity stimulated by high affinity binding of testosterone or dihydrotestosterone involves a dynamic NH2- and carboxyl-terminal (N/C) interaction between an AR NH2-terminal FXXLF motif (23FQNLF27) and a hydrophobic interaction surface in the ligand binding domain known as activation function 2 (AF2). The AR N/C interaction slows the dissociation rate of bound androgen, stabilizes AR and competitively inhibits activity from AF2. Functional significance of the androgen-dependent AR N/C interaction is supported by naturally occurring germline mutations in AF2 that decrease AR transcriptional activity and cause the androgen insensitivity syndrome by interfering with the N/C interaction without altering equilibrium androgen binding affinity. Gain-of-function AR somatic mutations in prostate cancer can enhance the AR N/C interaction in association with increased AR transcriptional activity. Melanoma antigen gene protein-A11 (MAGE-11) is an AR coactivator that competitively inhibits the AR N/C interaction by binding the AR FXXLF motif, but increases AR signaling through mechanisms that appear to contribute to the development and growth of prostate cancer.

Keywords

Androgen Receptor Ligand Binding Domain Mouse Mammary Tumor Virus Androgen Insensitivity Syndrome Complete Androgen Insensitivity Syndrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Laboratories for Reproductive Biology and the Lineberger Comprehensive Cancer CenterDepartments of Pediatrics, and the Department of Biochemistry and Biophysics University of North Carolina at Chapel HillNorth CarolinaUSA

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