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J. Biol. Chem. Nov (2002); 277(45):42852-8
A coregulatory role for the TRAP-mediator complex in androgen receptor-mediated gene expression.
Wang Q, Sharma D, Ren Y, Fondell JD
Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Abstract: 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.
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Chris Stark, Bobby-Joe Breitkreutz, Teresa Reguly, Lorrie Boucher, Ashton Breitkreutz, Mike Tyers.
Nucleic Acids Res. Jan 1;34:D535-9.