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 RIS Download
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