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ZIP kinase plays a crucial role in androgen receptor-mediated transcription

Oncogene volume 27, pages 3292–3300 (2008)Cite this article

Abstract

The androgen receptor (AR) is a ligand-dependent transcription factor that plays a crucial role in the development and homeostasis of the prostate and in prostate cancer. The transcriptional activity of AR is mediated by interaction with multiple co-activators, which serve in chromatin modification or remodeling, or provide a link between specific and general transcription factors. We have identified zipper interacting protein (ZIP) kinase as a novel transcriptional co-activator of the AR. ZIP kinase enhanced expression of AR-responsive promotor/luciferase reporter constructs in a hormone- and kinase-dependent manner. Similar results were obtained for glucocorticoid receptor but not for progesterone receptor and estrogen receptor. Following hormone treatment, AR and ZIP kinase formed physical complexes and associated with the promoter and enhancer of the prostate-specific antigen gene, as revealed by chromatin immunoprecipitation. Strikingly, depletion of ZIP kinase by siRNA led to significant reduction of AR-mediated transactivation. The interaction of ZIP kinase with AR seems to be mediated in part by apoptosis antagonizing transcription factor and in part by direct binding. Interestingly, AR was not phosphorylated by ZIP kinase in vitro, suggesting that it phosphorylates other co-activators or chromatin proteins.

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Acknowledgements

We thank Gerd Landsberg for excellent technical assistance. Dr Roland Schuele and Dr Ma Yin (University Hospital, Freiburg, Germany) for their hospitality and introduction to the ChIP technique and for the reporter plasmid PSA-enhancer-luc and expression plasmid for progesterone receptor; and Dr Maurizio Fanciulli (Regina Elena Cancer Institute, Rome, Italy) for antibodies against AATF/Che-1 and for providing the sequence for AATF/Che1-specific siRNA. This work was supported by the German Research Council Grant Sche246/16-1.

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  1. P Leister

    Present address: 2Current address: InVivo BioTech, Neuendorfstrasse, 24a, D-16761, Henningsdorf, Germany.,

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  1. Institute of Genetics, University of Bonn, Bonn, Germany

    P Leister, A Felten, A I Chasan & K H Scheidtmann

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Correspondence to K H Scheidtmann.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Leister, P., Felten, A., Chasan, A. et al. ZIP kinase plays a crucial role in androgen receptor-mediated transcription. Oncogene 27, 3292–3300 (2008). https://doi.org/10.1038/sj.onc.1210995

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