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Regulation of Androgen Receptor Activity by the Nuclear Receptor Corepressor SMRT

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Liao, Guoqing, Chen, Liuh-Yow, Zhang, Aihua, Godavarthy, Aparna, Xia, Fang, Ghosh, Jagadish Chandra, Li, Hui, Chen, J. Don·2003·Journal of Biological Chemistry
DOI 10.1074/jbc.m206374200
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Abstract

Androgen receptor (AR) is a hormone-regulated transcription factor that mediates a wide array of biological processes including sexual differentiation, spermatogenesis, and prostate cancer progression. The transcriptional activity of AR and other members of the nuclear receptor superfamily are modulated by coregulatory proteins. In this study, we have investigated the regulation of AR transcriptional activity by the silencing mediator for retinoid and thyroid hormone receptors (SMRT). We found that AR possesses an intrinsic transcriptional repression activity, and AR interacts directly with SMRT. One interacting surface on AR is mapped to the ligand-binding domain, and the presence of a DNA binding/hinge region enhances this interaction. The binding surface on SMRT is mapped to the C-terminal ID2 region, and mutation in the ID2 corepressor motif inhibits the interaction. Overexpression of SMRT inhibits dihydrotestosterone-dependent transactivation by AR and further suppresses the antiandrogen flutamide-mediated inhibition of AR activity. We provide evidence to suggest that the mechanisms of SMRT-mediated inhibition of AR activity involves inhibition of AR N/C interaction and competition with the p160 coactivator. Our data establish a significant role of SMRT in modulating AR transcriptional activity.

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Metadata

Authors
Liao, G., Chen, L.-Y., Zhang, A., Godavarthy, A., Xia, F., Ghosh, J. C., Li, H., & Chen, J. D.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2003-02
Volume
278
Issue
7
Pages
5052-5061
ISSN
0021-9258 (ISSN-L)
DOI
10.1074/jbc.m206374200
OpenAlex
W2018299273
Cited by
183
References
6
FWCI
13.04
Type
journal article
Language
en
Open access
hybrid
Licence

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CoChat. (2026). Citation check: Regulation of Androgen Receptor Activity by the Nuclear Receptor Corepressor SMRT. https://app.cochat.ai/papers/10.1074/jbc.m206374200
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Liao, G., Chen, L.-Y., Zhang, A., Godavarthy, A., Xia, F., Ghosh, J. C., Li, H., & Chen, J. D. (2003). Regulation of Androgen Receptor Activity by the Nuclear Receptor Corepressor SMRT. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m206374200

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