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The glycogen synthase kinase (GSK) 3β represses RNA polymerase I transcription

Oncogene volume 27, pages 5254–5259 (2008)Cite this article

Abstract

Several oncogenic proteins and tumour suppressors target the RNA polymerase I and interfere with rRNA synthesis. Here, we show that the glycogen synthase kinase (GSK) 3β, which phosphorylates the tumour suppressor PTEN (phosphatase and tensin homologue deleted on chromosome 10), is selectively enriched in nucleoli of RAS-transformed cells. Immunoprecipitation and chromatin immunoprecipitation assays performed on epithelial and endothelial cells transformed with oncogenic RAS show that GSK3β and PTEN are part of the same complex and associate with promoter and coding region of the rDNA. An active GSK3β mutant abolished nucleolar BrUTP incorporation and associated with the member of the selectivity factor 1 complex TAFI110. Finally, GSK3β inhibition upregulated 45S, 18S and 28S rRNA synthesis in RAS-transformed epithelial cells as revealed by semiquantitative real-time PCR and promoted cellular proliferation. Our results underscore a repressive function for GSK3β in rRNA biogenesis supporting its role as a tumour supressor.

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Acknowledgements

We thank J Arbiser (Emory University, USA) and H Beug (Institute of Molecular Pathology, Vienna) for providing EpRAS and SVR cells. This work was supported by grants from the Swedish Research Council (Vetenskapsrådet), Cancerfonden, the Lars Hiertas Minne Foundation and the Jeansson Foundation to PP.

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Author notes

  1. T Vincent and A Kukalev: These authors equally contributed to this work.

Authors and Affiliations

  1. Ludwig Institute for Cancer Research, Stockholm Branch, Karolinska Institutet, Stockholm, Sweden

    T Vincent & R Pettersson

  2. Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institute, Stockholm, Sweden

    A Kukalev & P Percipalle

  3. Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden

    M Andäng

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  1. T Vincent
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  2. A Kukalev
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  3. M Andäng
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  4. R Pettersson
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Corresponding author

Correspondence to P Percipalle.

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

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Vincent, T., Kukalev, A., Andäng, M. et al. The glycogen synthase kinase (GSK) 3β represses RNA polymerase I transcription. Oncogene 27, 5254–5259 (2008). https://doi.org/10.1038/onc.2008.152

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