A coregulatory role for the TRAP-mediator complex in androgen receptor-mediated gene expression

J Biol Chem. 2002 Nov 8;277(45):42852-8. doi: 10.1074/jbc.M206061200. Epub 2002 Sep 5.


The human thyroid hormone receptor-associated protein (TRAP)-Mediator complex was originally identified as a large multimeric complex that copurifies with the thyroid hormone receptor (TR) from HeLa cells and markedly enhances TR-mediated transcription in vitro. More recent studies have implicated TRAP-Mediator as a coactivator for a broad range of nuclear hormone receptors as well as other classes of transcriptional activators. Here we present evidence that TRAP-Mediator plays a functional role in androgen receptor (AR)-mediated transcription. We show that several subunits of the complex ligand-dependently coimmunoprecipitate with AR from both prostate cancer LNCaP cells and from HeLa cells stably transfected with AR. The 220-kDa subunit of the complex (TRAP220) can contact the ligand-binding domain of AR in vitro, possibly implicating TRAP220 involvement in targeting AR to the holocomplex. Consistent with a TRAP-Mediator coactivator role, transient overexpression of the TRAP220, TRAP170, and TRAP100 subunits enhanced ligand-dependent transcription by AR in cultured cells. Finally, chromatin immunoprecipitation assays show that TRAP220 is recruited to the androgen-responsive prostate-specific antigen gene promoter in vivo in ligand-stimulated LNCaP cells. Collectively, these data suggest that TRAP-Mediator may play an important coregulatory role in AR-mediated gene expression.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, Neoplasm / genetics*
  • Bacterial Proteins / metabolism*
  • Carrier Proteins*
  • Chromatin / physiology
  • Gene Expression Regulation, Neoplastic / physiology*
  • HeLa Cells
  • Humans
  • Male
  • Mediator Complex
  • Mediator Complex Subunit 1
  • Promoter Regions, Genetic
  • Prostate-Specific Antigen / genetics
  • Prostatic Neoplasms
  • Protein Subunits / metabolism
  • RNA-Binding Proteins / metabolism*
  • Receptors, Androgen / physiology*
  • Receptors, Thyroid Hormone / metabolism
  • Trans-Activators*
  • Transcription Factors / metabolism*
  • Tumor Cells, Cultured


  • Antigens, Neoplasm
  • Bacterial Proteins
  • Carrier Proteins
  • Chromatin
  • MED1 protein, human
  • MED24 protein, human
  • Med17 protein, human
  • Mediator Complex
  • Mediator Complex Subunit 1
  • MtrB protein, Bacteria
  • Protein Subunits
  • RNA-Binding Proteins
  • Receptors, Androgen
  • Receptors, Thyroid Hormone
  • Trans-Activators
  • Transcription Factors
  • Prostate-Specific Antigen