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.
Grierson
A J
AJ
Department of Neuroscience, The Institute of Psychiatry, London, UK.
Mootoosamy
R C
RC
Miller
C C
CC
D002478:Cells, Cultured; D005809:Genes, Regulator / Q000235:genetics*; D006801:Humans; D020966:Muscular Disorders, Atrophic / Q000503:physiopathology; D010455:Peptides / Q000235:genetics* / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics* / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid / Q000235:genetics*
D010455:Peptides; D016755:Proto-Oncogene Proteins c-jun; D011944:Receptors, Androgen; C097188:polyglutamine