The androgen receptor interacts with multiple regions of the large subunit of general transcription factor TFIIF

Jill Reid, I. Murray, K. Watt, Russell Betney, Iain Joseph McEwan

Research output: Contribution to journalArticle

45 Citations (Scopus)

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 languageEnglish
Pages (from-to)41247-41253
Number of pages6
JournalThe Journal of Biological Chemistry
Volume277
Issue number43
DOIs
Publication statusPublished - 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

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