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

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, 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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