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Distinct effects of PIAS proteins on androgen-mediated gene activation in prostate cancer cells

Oncogene volume 20, pages 3880–3887 (2001)Cite this article

Abstract

Androgen signaling influences the development and growth of prostate carcinoma. The transcriptional activity of androgen receptor (AR) is regulated by positive or negative transcriptional cofactors. We report here that PIAS1, PIAS3, and PIASy of the protein inhibitor of activated STAT (PIAS) family, which are expressed in human prostate, display distinct effects on AR-mediated gene activation in prostate cancer cells. While PIAS1 and PIAS3 enhance the transcriptional activity of AR, PIASy acts as a potent inhibitor of AR in prostate cancer cells. The effects of PIAS proteins on AR are competitive. PIASy binds to AR but does not affect the DNA binding activity of AR. An NH2-terminal LXXLL signature motif of PIASy, although not required for PIASy–AR interaction, is essential for the transrepression activity of PIASy. Our results identify PIASy as a transcriptional corepressor of AR and suggest that different PIAS proteins have distinct effects on AR signaling in prostate cancer cells.

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Acknowledgements

We thank C Sawyers for discussion and reading the manuscript; X Rao and M Sohn for technical assistance. B Liu is a Cancer Research Institute fellow. Supported by a grant from the NIH (AI43438).

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Authors and Affiliations

  1. Division of Hematology-Oncology, Department of Medicine, University of California, Los Angeles, 90095, California, CA, USA

    Mitchell Gross, Bin Liu & Ke Shuai

  2. Department of Biological Chemistry, University of California, Los Angeles, 90095, California, CA, USA

    Michael Carey & Ke Shuai

  3. Department of Pediatrics, The Laboratories for Reproductive Biology, University of North Carolina School of Medicine, Chapel Hill, 27599-7500, North Carolina, NC, USA

    Jiann-an Tan & Frank S French

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Gross, M., Liu, B., Tan, Ja. et al. Distinct effects of PIAS proteins on androgen-mediated gene activation in prostate cancer cells. Oncogene 20, 3880–3887 (2001). https://doi.org/10.1038/sj.onc.1204489

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