Evidence for a repressive function of the long polyglutamine tract in the human androgen receptor: possible pathogenetic relevance for the (CAG)n-expanded …
P Kazemi-Esfarjani, MA Trifiro… - Human molecular …, 1995 - academic.oup.com
P Kazemi-Esfarjani, MA Trifiro, L Pinsky
Human molecular genetics, 1995•academic.oup.comWe 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 …
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 …
Abstract
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 spinobulbar 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.
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