Characterization of Steroid Receptor RNA Activator Protein Function in Modulating the Estrogen Signaling Pathway
Abstract
The bi-faceted products of the Steroid receptor RNA activator gene (SRA1) consist of a functional RNA, which acts as a transcriptional co-activator and a protein (SRAP), that is conserved in chordates and which function remains elusive. Regarding the functional role of SRAP, we had determined through protein arrays that SRAP is able to interact with various transcription factors. Furthermore, we have established that SRAP is associated to chromatin in MCF-7 cells. We also examined the possible effect of SRAP recruitment on transcription using the potent GAL4-VP16 hybrid transcription activation system. We observed that SRA possesses a transcriptional repressive activity capable of inhibiting the GAL4-VP16 transcription activity. This SRAP transcriptional repressive potential is sensitive to trichostatin A (a HDAC inhibitor) treatment. In addition, SRAP is able to co-immunoprecipitate HDAC activity. Meanwhile, using splice-switching-oligonucleotides and real-time PCR, we observed that increasing the balance between non-coding SRA to coding-SRA led to an increase in ER-beta expression in T5 breast tumor cells. Further experiments confirm that it is SRAP rather than SRA integrates ER-beta expression. Finally, we found SRAP differentially regulates unbound and agonist/antagonist bound estrogen receptor alpha activity in an estrogen responsive elementdependent manner.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2008
- Accession Number
- ADA483730
Entities
People
- Yi Yan
Organizations
- University of Manitoba