Regulation of androgen receptor-mediated transcription by RPB5 binding protein URI/RMP

Paolo Mita, Jeffrey N. Savas, Nabil Djouder, John R. Yates, Susan Ha, Rachel Ruoff, Eric D. Schafler, Jerome C. Nwachukwu, Naoko Tanese, Nicholas J. Cowan, Jiri Zavadil, Michael J. Garabedian, Susan K. Logan*

*Corresponding author for this work

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Androgen receptor (AR)-mediated transcription is modulated by interaction with coregulatory proteins. We demonstrate that the unconventional prefoldin RPB5 interactor (URI) is a new regulator of AR transcription and is critical for antagonist (bicalutamide) action. URI is phosphorylated upon androgen treatment, suggesting communication between the URI and AR signaling pathways. Whereas depletion of URI enhances AR-mediated gene transcription, overexpression of URI suppresses AR transcriptional activation and anchorage-independent prostate cancer cell growth. Repression of AR-mediated transcription is achieved, in part, by URI binding and regulation of androgen receptor trapped clone 27 (Art-27), a previously characterized AR corepressor. Consistent with this idea, genome-wide expression profiling in prostate cancer cells upon depletion of URI or Art-27 reveals substantially overlapping patterns of gene expression. Further, depletion of URI increases the expression of the AR target gene NKX-3.1, decreases the recruitment of Art-27, and increases AR occupancy at the NKX-3.1 promoter. While Art-27 can bind AR directly, URI is bound to chromatin prior to hormone-dependent recruitment of AR, suggesting a role for URI in modulating AR recruitment to target genes.

Original languageEnglish (US)
Pages (from-to)3639-3652
Number of pages14
JournalMolecular and cellular biology
Volume31
Issue number17
DOIs
StatePublished - Sep 2011

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Regulation of androgen receptor-mediated transcription by RPB5 binding protein URI/RMP'. Together they form a unique fingerprint.

  • Cite this

    Mita, P., Savas, J. N., Djouder, N., Yates, J. R., Ha, S., Ruoff, R., Schafler, E. D., Nwachukwu, J. C., Tanese, N., Cowan, N. J., Zavadil, J., Garabedian, M. J., & Logan, S. K. (2011). Regulation of androgen receptor-mediated transcription by RPB5 binding protein URI/RMP. Molecular and cellular biology, 31(17), 3639-3652. https://doi.org/10.1128/MCB.05429-11