In Vitro regulation of reporter gene transcription by the androgen receptor AF1 domain

Muhammad Ansar Choudhry, Iain Joseph McEwan

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The androgen receptor (AR) is a ligand-activated transcription factor that regulates gene expression in response to the steroids testosterone and dilhydrotestosterone. AR-dependent gene expression is likely to play an important role in a number of receptor-associated disorders, such as prostate cancer, spinal bulbar muscular atrophy, male type baldness and hirsutism. The AR contains two transactivation domains, termed AF1 (activation function 1) located in the N-terminus and AF2 (activation function 2) in the C-terminal ligand-binding domain. AF2 exhibits weak transcriptional activity, whereas AF1 is a strong regulator of transcription. Transcriptional regulation by AF1 is thought to be modulated by a number of proteins that interact with this region, and by post-translational modifications. our focus is on the N-terminal-interacting proteins and their regulation of transcription via interaction with the receptor. To better understand the mechanism of AR-AF1 action, we have reconstituted AR activity in HeLa nuclear extracts using a unique dual reporter gene assay. Multiple LexA-binding sites in the promoter allow transcription to be driven by a recombinant AR-AF1-Lex fusion protein. The findings from initial experiments suggest an increase in transcription initiation and elongation rates by AR-AF1-Lex. The role of protein-protein interactions involving co-activators and basal transcription factors and AR-AF1 activity are discussed.

Original languageEnglish
Pages (from-to)1103-1106
Number of pages3
JournalBiochemical Society Transactions
Volume32
DOIs
Publication statusPublished - 2004

Keywords

  • co-activator
  • protein-protein interaction
  • steroid receptor
  • transactivation domain
  • THIIF
  • FACTOR-TFIIF
  • DIFFERENTIATION
  • IDENTIFICATION
  • ELONGATION
  • EFFICIENCY
  • INTERACTS
  • REGIONS
  • COMPLEX
  • BONE

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