Structural and functional alterations in the androgen receptor in spinal bulbar muscular atrophy.
The androgen receptor is a member of the nuclear receptor superfamily, and regulates gene expression in response to the steroid hormones testosterone and dihydrotestosterone. Mutations in the receptor have been correlated with a diverse range of clinical conditions, including androgen insensitivity, prostate cancer and spinal bulbar muscular atrophy, a neuromuscular degenerative condition. The latter is caused by expansion of a polyglutamine repeat within the N-terminal domain of the receptor. Thus the androgen receptor is one of a growing number of neurodegenerative disease-associated proteins, including huntingtin (Huntington's disease), ataxin-1 (spinocerebellar ataxia, type 1) and ataxin-3 (spinocerebellar ataxia, type 3), which show expansion of CAG triplet repeats. Although widely studied, the functions of huntingtin, ataxin-1 and ataxin-3 remain unknown. The androgen receptor, which has a well-recognized function in gene regulation, provides a unique opportunity to investigate the functional significance of poly(amino acid) repeats in normal and disease states.
McEwan
I J
IJ
Department of Molecular and Cell Biology, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, U.K. iain.mcewan@abdn.ac.uk
D000818:Animals; D006801:Humans; D008297:Male; D009134:Muscular Atrophy, Spinal / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011944:Receptors, Androgen / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship; D019680:Trinucleotide Repeat Expansion / Q000235:genetics
D010455:Peptides; D011944:Receptors, Androgen; C097188:polyglutamine