The AR (androgen receptor) is a ligand-activated transcription factor that mediates the action of the steroids testosterone and dihydrotestosterone. Alterations in the AR gene result in a number of clinical disorders, including: androgen-insensitivity, which leads to disruption of male development; prostate cancer; and a neuromuscular degenerative condition termed spinal bulbar muscular atrophy or Kennedy's disease. The AR gene is X-linked and the protein is coded for by eight exons, giving rise to a C-terminal LBD (ligand-binding domain; exons 4–8), linked by a hinge region (exon 4) to a Zn-finger DBD (DNA-binding domain; exons 2 and 3) and a large structurally distinct NTD (N-terminal domain; exon 1). Identification and characterization of mutations found in prostate cancer and Kennedy's disease patients have revealed the importance of structural dynamics in the mechanisms of action of receptors. Recent results from our laboratory studying genetic changes in the LBD and the structurally flexible NTD will be discussed.
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December 2006
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Conference Article|
October 25 2006
Structural dynamics of the human androgen receptor: implications for prostate cancer and neurodegenerative disease
J. Duff;
J. Duff
1School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, U.K.
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P. Davies;
P. Davies
1School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, U.K.
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K. Watt;
K. Watt
1School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, U.K.
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I.J. McEwan
I.J. McEwan
1
1School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, U.K.
1To whom correspondence should be addressed (email iain.mcewan@abdn.ac.uk).
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Publisher: Portland Press Ltd
Received:
July 31 2006
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2006 The Biochemical Society
2006
Biochem Soc Trans (2006) 34 (6): 1098–1102.
Article history
Received:
July 31 2006
Citation
J. Duff, P. Davies, K. Watt, I.J. McEwan; Structural dynamics of the human androgen receptor: implications for prostate cancer and neurodegenerative disease. Biochem Soc Trans 1 December 2006; 34 (6): 1098–1102. doi: https://doi.org/10.1042/BST0341098
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