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PIASy-mediated repression of the androgen receptor is independent of sumoylation

Oncogene volume 23, pages 3059–3066 (2004)Cite this article

Abstract

PIASy, a member of the protein inhibitor of activated STAT (PIAS) family, represses the transcriptional activity of the androgen receptor (AR). In this report, we investigate the mechanism of PIASy-mediated repression of AR. We show that AR binds to the RING-finger like domain of PIASy. PIASy contains two transcriptional repression domains, RD1 and RD2. RD1, but not RD2, is required for PIASy-mediated repression of AR. We show that the RD1 domain binds HDAC1 and HDAC2 and that HDAC activity is required for PIASy-mediated AR repression. PIAS proteins possess small ubiquitin-related modifier (SUMO) E3 ligase activity. Conjugation of SUMO-1 to AR has been implicated in the regulation of AR activity. We examine if the SUMO ligase activity of PIASy is required for PIASy to repress AR. We show that a mutant PIASy, defective in promoting sumoylation, retains the ability to repress AR transcription. In addition, mutation of all the known sumoylation acceptor sites of AR does not affect the transrepression activity of PIASy on AR. Our results suggest that PIASy may repress AR by recruiting histone deacetylases, independent of its SUMO ligase activity.

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Acknowledgements

We thank Bin Liu and Johanna ten Hoeve for comments and Michael Carey for providing plasmids and helpful discussions. Supported by grants from NIH (AI39612, CA32737), US Army Medical Research and Materiel Command (DAMD17-01-1-0036), and CaP CURE Foundation to KS and NIH (DK64379) to MG.

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Author notes

  1. Mitchell Gross and Randy Yang: These authors contributed equally to this manuscript.

Authors and Affiliations

  1. Division of Hematology-Oncology, Department of Medicine, University of California, 11-934 Factor Bldg, 10833 Le Conte Avenue, Los Angeles, 90095-1678, CA, USA

    Mitchell Gross, Christina Gasper & Ke Shuai

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

    Randy Yang & Ke Shuai

  3. Louis Warschaw Prostate Cancer Center, Cedars-Sinai Medical Center, 8631 W. Third Street, Suite 1001E, Los Angeles, 90048, CA, USA

    Mitchell Gross & Irina Top

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  1. Mitchell Gross
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Correspondence to Ke Shuai.

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Gross, M., Yang, R., Top, I. et al. PIASy-mediated repression of the androgen receptor is independent of sumoylation. Oncogene 23, 3059–3066 (2004). https://doi.org/10.1038/sj.onc.1207443

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