Evidence for a repressive function of the long polyglutamine tract in the human androgen receptor: possible pathogenetic relevance for the (CAG)n-expanded neuronopathies.
We have reported that polyglutamine (polyGln)-expanded human androgen receptors (hAR) have reduced transactivational competence in transfected cells. We presumed that maximal hAR transactivation requires a normal-size polyGln tract. Here we report, however, that hAR transactivity and polyGln-tract length are related inversely: n = 0 > 12 > 20 > 40 > 50. Thus, a normal-size polyGln tract represses the transactivational competence of a polyGln-free hAR, and polyGln expansion increases that negative effect. This observation has pathogenetic implications for X-linked spinobular muscular atrophy (Kennedy syndrome), and possibly for the autosomal dominant central neuronopathies associated with (CAG)n expansion in the translated portion of four different genes.
Kazemi-Esfarjani
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P
Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, Montreal, Quebec, Canada.
Trifiro
M A
MA
Pinsky
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L
D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D018274:Electroporation; D005973:Glutamine / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D009422:Nervous System Diseases / Q000235:genetics*; D011131:Polyribonucleotides / Q000235:genetics; D011944:Receptors, Androgen / Q000235:genetics*; D015533:Transcriptional Activation
D017931:DNA Primers; D011131:Polyribonucleotides; D011944:Receptors, Androgen; D005973:Glutamine