p53 represses ribosomal gene transcription (original) (raw)

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• Published: 08 February 1999

Oncogene volume 18, pages 1119–1124 (1999)Cite this article

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Abstract

Induction of the tumor suppressor protein p53 restricts cellular proliferation. Since actively growing cells require the ongoing synthesis of ribosomal RNA to sustain cellular biosynthesis, we studied the effect of p53 on ribosomal gene transcription by RNA polymerase I (Pol I). We have measured rDNA transcriptional activity in different cell lines which either lack or overexpress p53 and demonstrate that wild-type but not mutant p53 inhibits cellular pre-rRNA synthesis. Conversely, pre-rRNA levels are elevated both in cells which express mutant p53 and in fibroblasts from p53 knock-out mice. Transient transfection assays with a set of rDNA deletion mutants demonstrate that intergenic spacer sequences are dispensable and the minimal rDNA promoter is sufficient for p53-mediated repression of Pol I transcription. However, in a cell-free transcription system, recombinant p53 does not inhibit rDNA transcription, indicating that p53 does not directly interfere with the basal Pol I transcriptional machinery. Thus, repression of Pol I transcription by p53 may be a consequence of p53-induced growth arrest.

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Acknowledgements

We are grateful to M Frey and H Zentgraf for generous gifts of purified bacterial p53. Furthermore, we thank M Oren for cell lines (MCO1 and MCO1/cG9-6) and expression vectors encoding wtp53 and p53Cys270, A Levine for (10)1 cells, T Jacks for p53−/− and p53+/+ primary fibroblasts and M Agarwal and GR Stark for TR9-7 cells. This work was supported by the Deutsche Forschungsgemeinschaft and the Fonds der Chemischen Industrie.

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1. Division of Molecular Biology of the Cell II, German Cancer Research Center, Heidelberg, 69120, Germany
   Andreja Budde & Ingrid Grummt

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1. Andreja Budde
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2. Ingrid Grummt
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Budde, A., Grummt, I. p53 represses ribosomal gene transcription.Oncogene 18, 1119–1124 (1999). https://doi.org/10.1038/sj.onc.1202402

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• Received: 23 June 1998
• Revised: 07 September 1998
• Accepted: 07 September 1998
• Published: 08 February 1999
• Issue Date: 28 January 1999
• DOI: https://doi.org/10.1038/sj.onc.1202402

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