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    Regulation of androgen receptor activity by the nuclear receptor corepressor SMRT

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    Authors
    Liao, Guoqing
    Chen, Liuh-Yow
    Zhang, Aihua
    Godavarthy, Aparna
    Xia, Fang
    Ghosh, Jagadish C.
    Li, Hui
    Chen, J. Don
    UMass Chan Affiliations
    Department of Cancer Biology
    Department of Biochemistry and Molecular Pharmacology
    Document Type
    Journal Article
    Publication Date
    2002-11-21
    Keywords
    DNA-Binding Proteins
    Gene Expression Regulation
    Hela Cells
    Humans
    Mutation
    Receptors, Androgen
    Recombinant Proteins
    Repressor Proteins
    Signal Transduction
    Transcription, Genetic
    Life Sciences
    Medicine and Health Sciences
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    Link to Full Text
    http://dx.doi.org/10.1074/jbc.M206374200
    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.
    Source
    J Biol Chem. 2003 Feb 14;278(7):5052-61. Epub 2002 Nov 18. Link to article on publisher's site
    DOI
    10.1074/jbc.M206374200
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/42370
    PubMed ID
    12441355
    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1074/jbc.M206374200
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