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

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.

Pubmed ID: 12218053


  • Wang Q
  • Sharma D
  • Ren Y
  • Fondell JD


The Journal of biological chemistry

Publication Data

November 8, 2002

Associated Grants

  • Agency: NIDDK NIH HHS, Id: DK60883

Mesh Terms

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