Abstract
The multifunctional protein Yin Yang 1 (YY1) has an important role in epigenetic regulation of gene expression. YY1 is highly expressed in various types of cancers, including prostate cancer. Currently, the mechanism underlying the functional role of YY1 in prostate tumorigenesis remains unclear. In this report, we investigated the functional interplay between YY1 and androgen receptor (AR), and the effect of YY1 on AR-mediated transcription. We found that YY1 physically interacts with AR both in a cell-free system and in cultured cells. YY1 is required for the optimal transcriptional activity of AR in promoting the transcription of the prostate-specific antigen (PSA) promoter. However, ectopic YY1 expression in LNCaP cells did not further enhance the reporter driven by the PSA promoter, suggesting that an optimal level of YY1 is already established in prostate tumor cells. Consistently, YY1 depletion in LNCaP cells reduced endogenous PSA levels, but overexpressed YY1 did not significantly increase PSA expression. We also observed that YY1–AR interaction is essential to YY1-mediated transcription activity of AR and YY1 is a necessary component in the complex binding to the androgen response element. Thus, our study demonstrates that YY1 interacts with AR and regulates its transcriptional activity.
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Acknowledgements
We thank Dr Purnima Dubey and Ms Karen Klein for critical reading of the article. We also thank Dr Suzy Torti and Dr Wei Wang for providing the access to some equipment, and Dr Kazushi Inoue for the EMSA protocol. The support for the work came from the grant of American Cancer Society (RSG-09-082-01-MGO) and the startup fund from the Department of Cancer Biology and Comprehensive Cancer Center of Wake Forest University to GS. PC is supported by NCI training Grant 5T32CA079448-09.
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Deng, Z., Wan, M., Cao, P. et al. Yin Yang 1 regulates the transcriptional activity of androgen receptor. Oncogene 28, 3746–3757 (2009). https://doi.org/10.1038/onc.2009.231
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DOI: https://doi.org/10.1038/onc.2009.231
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