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

T Vincent1, A Kukalev, M Andäng

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

Oncogene
|May 21, 2008
PubMed

Insights

Glycogen synthase kinase 3 beta (GSK3beta) is enriched in nucleoli of RAS-transformed cells, where it represses ribosomal RNA (rRNA) synthesis. Inhibiting GSK3beta promotes rRNA synthesis and cell proliferation, supporting its tumor suppressor role.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Oncogenic proteins and tumor suppressors can target RNA polymerase I, affecting ribosomal RNA (rRNA) synthesis.
  • PTEN (phosphatase and tensin homologue deleted on chromosome 10) is a tumor suppressor phosphorylated by GSK3beta.

Purpose of the Study:

  • To investigate the role of glycogen synthase kinase 3 beta (GSK3beta) in RAS-transformed cells.
  • To elucidate the mechanism by which GSK3beta influences rRNA synthesis and cell proliferation.

Main Methods:

  • Immunoprecipitation and chromatin immunoprecipitation assays were used to study protein complexes and DNA association.
  • Quantitative real-time PCR was employed to measure rRNA synthesis.
  • Cellular proliferation assays were conducted.

Main Results:

  • GSK3beta is selectively enriched in nucleoli of RAS-transformed cells.
  • GSK3beta and PTEN form a complex that associates with rDNA.
  • Active GSK3beta mutant abolished nucleolar rRNA synthesis and associated with TAF(I)110.
  • GSK3beta inhibition upregulated rRNA synthesis and promoted proliferation in RAS-transformed cells.

Conclusions:

  • GSK3beta plays a repressive role in rRNA biogenesis.
  • These findings support a tumor suppressor function for GSK3beta in the context of RAS-driven cancers.

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