Structural and functional alterations in the androgen receptor in spinal bulbar muscular atrophy.

Abstract

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.

• Authors: I J McEwan
• Journal: Biochemical Society transactions (Biochem Soc Trans) Vol. 29 Issue Pt 2 Pg. 222-7 (May 2001) ISSN: 0300-5127 [Print] England
• PMID: 11356158 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Peptides
• Receptors, Androgen
• polyglutamine

Topics

• Animals
• Humans
• Male
• Muscular Atrophy, Spinal (genetics, metabolism)
• Mutation (genetics)
• Peptides (genetics, metabolism)
• Protein Binding
• Protein Structure, Tertiary
• Receptors, Androgen (chemistry, genetics, metabolism)
• Structure-Activity Relationship
• Trinucleotide Repeat Expansion (genetics)