The androgen receptor interacts with multiple regions of the large subunit of general transcription factor TFIIF.
The androgen receptor (AR) is a ligand-activated transcription factor that regulates genes important for male development and reproductive function. The main determinants for the transactivation function lie within the structurally distinct amino-terminal domain. Previously we identified an interaction between the AR-transactivation domain (amino acids 142-485) and the general transcription factor TFIIF (McEwan, I. J., and Gustafsson, J.-A. (1997) Proc. Natl. Acad. Sci. U. S. A. 94, 8485-8490). We have now mapped the binding sites for the AR-transactivation domain within the RAP74 subunit of TFIIF. Both the amino-terminal 136 amino acids and the carboxyl-terminal 155 amino acids of RAP74 interacted with the AR-transactivation domain and were able to rescue basal transcription after squelching by the AR polypeptide. Competition experiments demonstrated that the AR could interact with the holo-TFIIF protein and that the carboxyl terminus of RAP74 represented the principal receptor-binding site. Point mutations within AR-transactivation domain distinguished the binding sites for RAP74 and the p160 coactivator SRC-1a and identified a single copy of a six amino acid repeat motif as being important for RAP74 binding. These data indicate that the AR-transactivation domain can potentially make multiple protein-protein interactions with coactivators and components of the general transcriptional machinery in order to regulate target gene expression.
Reid
James
J
Department of Molecular and Cell Biology, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, UK.
Murray
Ian
I
Watt
Kate
K
Betney
Russell
R
McEwan
Iain J
IJ
D001483:Base Sequence; D001665:Binding Sites; D017931:DNA Primers; D016297:Mutagenesis, Site-Directed; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D019473:Transcription Factors, TFII / Q000737:chemistry / Q000378:metabolism*
D017931:DNA Primers; D011944:Receptors, Androgen; D019473:Transcription Factors, TFII; C056604:transcription factor TFIIF