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MedicineStress Physiology

Characterization of Steroid Receptor RNA Activator Protein Function in Modulating the Estrogen Signaling Pathway

Authors: Yi Yan; MANITOBA UNIV WINNIPEG
Abstract:
Steroid receptor RNA activator (SRA) was shown to differ from all previously characterized co-activators as it was demonstrated to function as a RNA rather than a protein molecule. We have however demonstrated that this once thought non-coding RNA encodes a well conserved protein (SRAP). The aims of this year are mainly on identification of SRAP-interacting Proteins and how SRAP interacts with transcriptional regulators to modulates of transcription as well as the respective impacts of SRA RNA and SRA protein on the ER signaling pathway. We have determined through protein arrays that SRAP is indeed able to directly 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-VPI6 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. And SRAP is able to co-immunoprecipitate HDAC activity. Meanwhile we have also investigated the possible mechanism of intron-1 retention as a participating to the generation of coding and non coding SRA RNAs.

Limitations: APPROVED FOR PUBLIC RELEASE
Description: Annual summary rept. 21 Feb 2006-20 Feb 2007
Pages: 122
Report Date: MAY 2007
Contract Number: W81XWH0510245
Report Number: A038174
Keywords relating to this report:
*BREAST CANCER
*CELLS(BIOLOGY)
*CELLS_BIOLOGY_
*ESTROGENS
*PROTEINS
*RIBONUCLEIC ACIDS
*STEROIDS
ACTIVATION
CHROMATIN
MOLECULAR BIOLOGY
MOLECULES
PROGESTERONE
TRANSCRIPTION_GENETICS_
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