Characterization of Factors Affecting Androgen Receptor Transcriptional Regulation in Prostate Cancer
Abstract
The androgen receptor (AR) is a ligand-regulated transcription factor that stimulates cell growth and differentiation in androgen-responsive tissues. The AR N-terminus contains two activation functions (AF-1a and AF-1b) that are necessary for maximal transcriptional enhancement by the receptor, however, the mechanisms and components regulating AR transcriptional activation are not fully understood. We sought to identify novel factors that interact with the AR N-terminus from an androgen-stimulated human prostate cancer cell library using a yeast two-hybrid approach. A 157-amino acid protein termed ART-27 was cloned and shown to interact predominantly with the AR153-336, containing AF-1a and a part of AF-1b, localize to the nucleus and increase the transcriptional activity of AR when overexpressed in cultured mammalian cells. ART-27 also enhanced the transcriptional activation by AR153-336 fused to LexA DNA binding domain, but not other AR N-terminal subdomains, suggesting that ART-27 exerts its effect via an interaction with a defined region of the AR N-terminus. ART-27 interacts with AR in nuclear extracts from LNCaP cells in a ligand-independent fashion. Interestingly, velocity gradient sedimentation of HeLa nuclear extracts suggests that native ART-27 is part of a multiprotein complex. Thus, ART-27 is a novel cofactor that interacts with the AR N-terminus.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2002
- Accession Number
- ADA405342
Entities
People
- Michael J. Garabedian
Organizations
- New York University