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

T. Vincent, A. Kukalev, M. Andäng, R. Pettersson, Piergiorgio Percipalle

    Research output: Contribution to journalArticle

    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 TAF I110. 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.

    Original languageEnglish (US)
    Pages (from-to)5254-5259
    Number of pages6
    JournalOncogene
    Volume27
    Issue number39
    DOIs
    StatePublished - Sep 4 2008

    Fingerprint

    RNA Polymerase I
    Glycogen Synthase Kinase 3
    Epithelial Cells
    PTEN Phosphohydrolase
    Tumor Suppressor Proteins
    Chromosomes, Human, Pair 10
    Chromatin Immunoprecipitation
    Ribosomal DNA
    Immunoprecipitation
    Genetic Promoter Regions
    Real-Time Polymerase Chain Reaction
    Neoplasms
    Endothelial Cells
    Cell Proliferation
    Tensins

    Keywords

    • Cell proliferation
    • GSKβ
    • Pol I transcription
    • PTEN
    • rDNA
    • Tumour suppressors

    ASJC Scopus subject areas

    • Molecular Biology
    • Cancer Research
    • Genetics

    Cite this

    Vincent, T., Kukalev, A., Andäng, M., Pettersson, R., & Percipalle, P. (2008). The glycogen synthase kinase (GSK) 3β represses RNA polymerase I transcription. Oncogene, 27(39), 5254-5259. https://doi.org/10.1038/onc.2008.152

    The glycogen synthase kinase (GSK) 3β represses RNA polymerase I transcription. / Vincent, T.; Kukalev, A.; Andäng, M.; Pettersson, R.; Percipalle, Piergiorgio.

    In: Oncogene, Vol. 27, No. 39, 04.09.2008, p. 5254-5259.

    Research output: Contribution to journalArticle

    Vincent, T, Kukalev, A, Andäng, M, Pettersson, R & Percipalle, P 2008, 'The glycogen synthase kinase (GSK) 3β represses RNA polymerase I transcription', Oncogene, vol. 27, no. 39, pp. 5254-5259. https://doi.org/10.1038/onc.2008.152
    Vincent T, Kukalev A, Andäng M, Pettersson R, Percipalle P. The glycogen synthase kinase (GSK) 3β represses RNA polymerase I transcription. Oncogene. 2008 Sep 4;27(39):5254-5259. https://doi.org/10.1038/onc.2008.152
    Vincent, T. ; Kukalev, A. ; Andäng, M. ; Pettersson, R. ; Percipalle, Piergiorgio. / The glycogen synthase kinase (GSK) 3β represses RNA polymerase I transcription. In: Oncogene. 2008 ; Vol. 27, No. 39. pp. 5254-5259.
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