Implications of a polyglutamine tract in the function of the human androgen receptor.
The androgen receptor (AR) is a ligand-dependent transcription factor and belongs to the nuclear receptor family. The AR gene contains a long polymorphic CAG repeat, coding for a polyglutamine tract. In the full size AR, the deletion of the polyglutamine tract results in an increase in the transactivation through canonical AREs. However, this effect is clearly dependent on the response elements, since it is not observed on selective elements. In our assays, a deletion of the repeat positively affected the interactions of the ligand-binding domain with the amino-terminal domain as well as the recruitment of the p160 coactivator SRC-1e to the amino-terminal domain of the AR. This is reflected by an enhanced coactivation of the AR by SRC-1e.
Callewaert
Leen
L
Division of Biochemistry, Faculty of Medicine, Campus Gasthuisberg O/N, University of Leuven, O/N, Herestraat 49, B-3000, Louvain, Belgium.
Christiaens
Valerie
V
Haelens
Annemie
A
Verrijdt
Guy
G
Verhoeven
Guido
G
Claessens
Frank
F
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D019556:COS Cells; D051548:Histone Acetyltransferases; D006801:Humans; D066298:In Vitro Techniques; D056920:Nuclear Receptor Coactivator 1; D010455:Peptides / Q000737:chemistry* / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D017434:Protein Structure, Tertiary; D011944:Receptors, Androgen / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D025842:SUMO-1 Protein / Q000378:metabolism; D017384:Sequence Deletion; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation
D010455:Peptides; D011944:Receptors, Androgen; D011994:Recombinant Proteins; D025842:SUMO-1 Protein; D014157:Transcription Factors; C097188:polyglutamine; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1