Abstract
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.-Angstrom. (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-la 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.
Original language | English |
---|---|
Pages (from-to) | 41247-41253 |
Number of pages | 6 |
Journal | The Journal of Biological Chemistry |
Volume | 277 |
Issue number | 43 |
DOIs | |
Publication status | Published - Oct 2002 |
Keywords
- AMINO-TERMINAL DOMAIN
- LIGAND-BINDING DOMAIN
- HUMAN GLUCOCORTICOID RECEPTOR
- AR SUPPRESSES TRANSCRIPTION
- PROSTATE-CANCER CELLS
- RNA-POLYMERASE-II
- MEDIATED TRANSCRIPTION
- RESPONSIVE ELEMENT
- COACTIVATOR
- ACTIVATION