Identification and characterization of ART-27, a novel coactivator for the androgen receptor N terminus

Steven M. Markus, Samir S. Taneja, Susan K. Logan, Wenhui Li, Susan Ha, Adam B. Hittelman, Inez Rogatsky, Michael J. Garabedian

    Research output: Contribution to journalArticle

    Abstract

    The androgen receptor (AR) is a ligand-regulated transcription factor that stimulates cell growth and differentiation in androgen-responsive tissues. The AR N terminus contains two activation functions (AF-1a and AF-1b) that are necessary for maximal transcriptional enhancement by the receptor; however, the mechanisms and components regulating AR transcriptional activation are not fully understood. We sought to identify novel factors that interact with the AR N terminus from an androgen-stimulated human prostate cancer cell library using a yeast two-hybrid approach designed to identify proteins that interact with transcriptional activation domains. A 157-amino acid protein termed ART-27 was cloned and shown to interact predominantly with the AR153-336, containing AF-1a and a part of AF-1b, localize to the nucleus and increase the transcriptional activity of AR when overexpressed in cultured mammalian cells. ART-27 also enhanced the transcriptional activation by AR153-336 fused to the LexA DNA-binding domain but not other AR N-terminal subdomains, suggesting that ART-27 exerts its effect via an interaction with a defined region of the AR N terminus. ART-27 interacts with AR in nuclear extracts from LNCaP cells in a ligand-independent manner. Interestingly, velocity gradient sedimentation of HeLa nuclear extracts suggests that native ART-27 is part of a multiprotein complex. ART-27 is expressed in a variety of human tissues, including sites of androgen action such as prostate and skeletal muscle, and is conserved throughout evolution. Thus, ART-27 is a novel cofactor that interacts with the AR N terminus and plays a role in facilitating receptor-induced transcriptional activation.

    Original languageEnglish (US)
    Pages (from-to)670-682
    Number of pages13
    JournalMolecular biology of the cell
    Volume13
    Issue number2
    DOIs
    StatePublished - Mar 4 2002

    ASJC Scopus subject areas

    • Molecular Biology
    • Cell Biology

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  • Cite this

    Markus, S. M., Taneja, S. S., Logan, S. K., Li, W., Ha, S., Hittelman, A. B., Rogatsky, I., & Garabedian, M. J. (2002). Identification and characterization of ART-27, a novel coactivator for the androgen receptor N terminus. Molecular biology of the cell, 13(2), 670-682. https://doi.org/10.1091/mbc.01-10-0513