Characterization of the two coactivator-interacting surfaces of the androgen receptor and their relative role in transcriptional control.
The androgen receptor interacts with the p160 coactivators via two surfaces, one in the ligand binding domain and one in the amino-terminal domain. The ligand binding domain interacts with the nuclear receptor signature motifs, whereas the amino-terminal domain has a high affinity for a specific glutamine-rich region in the p160s. We here describe the implication of two conserved motifs in the latter interaction. The amino-terminal domain of the androgen receptor is a very strong activation domain constituent of Tau5, which is mainly active in the absence of the ligand binding domain, and Tau1, which is only active in the presence of the ligand binding domain. Both domains are, however, implicated in the recruitment of the p160s. Mutation analysis of the p160s has shown that the relative contribution of the two recruitment mechanisms via the signature motifs or via the glutamine-rich region depend on the nature of the enhancers tested. We propose, therefore, that the androgen receptor-coactivator complex has several alternative conformations, depending partially on the context of the enhancer.
Christiaens
Valerie
V
Division of Biochemistry, Faculty of Medicine, Campus Gasthuisberg, University of Leuven, Herestraat 49, B-3000 Leuven, Belgium.
Bevan
Charlotte L
CL
Callewaert
Leen
L
Haelens
Anna
A
Verrijdt
Guy
G
Rombauts
Wilfried
W
Claessens
Frank
F
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D019556:COS Cells; D004252:DNA Mutational Analysis; D005786:Gene Expression Regulation; D051548:Histone Acetyltransferases; D008024:Ligands; D008156:Luciferases / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D056920:Nuclear Receptor Coactivator 1; D051958:Nuclear Receptor Coactivator 2; D056921:Nuclear Receptor Coactivator 3; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011944:Receptors, Androgen / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry; D014158:Transcription, Genetic; D014162:Transfection; D015003:Yeasts / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
D008024:Ligands; D051958:Nuclear Receptor Coactivator 2; D011944:Receptors, Androgen; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D016875:tau Proteins; D008156:Luciferases; D051548:Histone Acetyltransferases; D056920:Nuclear Receptor Coactivator 1; D056921:Nuclear Receptor Coactivator 3; D001616:beta-Galactosidase