TAF1, From a General Transcription Factor to Modulator of Androgen Receptor in Prostate Cancer
Abstract
The androgen receptor (AR) is a ligand-activated transcription factor that is essential for development and progression of prostate cancer. Using the N-terminus of AR as bait in the repressed transactivator yeast two-hybrid system, TATA binding protein-associated factor 1 (TAF1) was identified. TAF1, a multifunctional protein that contains acetylation, ubiquitin activating and kinase domains, can interact with several proteins to promote or suppress gene transcription. In the present study, using GST pull-down assay we confirmed that TAF1 binds to NTD of AR through the E1/E2 and HAT domains. We demonstrated by co-immunoprecipitation and ChIP assays that TAF1 and AR bind in the nucleus and associate with an androgen response element (ARE) at the proximal promoter of the prostate specific antigen (PSA) gene in the presence of androgen. In addition, we found that TAF1 acts as a coactivator and enhances AR transcriptional activity through its NTK and E1/E2 domains without influencing the general transcriptional activity of a non-androgen responsive promoter. By using in-cell and in-tube ubiquitination assays, our finding also suggested that TAF1 could ubiqinate AR.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2009
- Accession Number
- ADA502641
Entities
People
- Paul Rennie
- Peyman Tavassoli
Organizations
- University of British Columbia