title: The glycogen synthase kinase (GSK) 3beta represses RNA polymerase I transcription.
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) 3beta, 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 GSK3beta and PTEN are part of the same complex and associate with promoter and coding region of the rDNA. An active GSK3beta mutant abolished nucleolar BrUTP incorporation and associated with the member of the selectivity factor 1 complex TAF(I)110. Finally, GSK3beta 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 GSK3beta in rRNA biogenesis supporting its role as a tumour supressor.
authors.affiliation: Ludwig Institute for Cancer Research, Stockholm Branch, Karolinska Institutet, Stockholm, Sweden.
authors.forename: T
authors.initials: T
authors.lastname: Vincent
authors.forename: A
authors.initials: A
authors.lastname: Kukalev
authors.forename: M
authors.initials: M
authors.lastname: Andäng
authors.forename: R
authors.initials: R
authors.lastname: Pettersson
authors.forename: P
authors.initials: P
authors.lastname: Percipalle
mesh_terms: D002466:Cell Nucleolus / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D012318:RNA Polymerase I / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D012318:RNA Polymerase I; D051059:PTEN Phosphohydrolase