The glycogen synthase kinase (GSK) 3β 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) 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. © 2008 Macmillan Publishers Limited All rights reserved.