Polyglutamine repeat length influences human androgen receptor/c-Jun mediated transcription

The androgen receptor and c-Jun are known to interact to modulate each others transcriptional activities. The androgen receptor contains a polymorphic polyglutamine repeat and expansion of this repeat to beyond approximately 40 causes spinobulbar muscular atrophy (SBMA; also known as Kennedy's disease), a genetic form of motor neurone disease. Here we show that the size of this polyglutamine tract influences both c-Jun regulation of androgen receptor-mediated transcription and androgen receptor regulation of c-Jun activity. c-Jun is a key mediator of neuronal survival and death by apoptosis. Inappropriate interactions between c-Jun and androgen receptors containing pathological length glutamine repeats may therefore be part of the pathogenic process in SBMA. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.