Cited by 157Cancer-related Molecular PathwaysGenomics and Chromatin DynamicsNuclear Structure and Function

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p53 represses ribosomal gene transcription

Budde, Andreja, Grummt, Ingrid·1999·Oncogene

DOI 10.1038/sj.onc.1202402

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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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Authors: Budde, A., & Grummt, I.
Affiliations: German Cancer Research Center (DE)
ORCID: Grummt, Ingrid
Venue: Oncogene
Publisher: Springer Science and Business Media LLC
Published: 1999-01-28
Volume: 18
Issue: 4
Pages: 1119-1124
ISSN: 0950-9232 (ISSN-L)
1476-5594
DOI: 10.1038/sj.onc.1202402
OpenAlex: W2076958652
Cited by: 157
References: 37
Citations by year: 2026: 2 · 2025: 3 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 5 · 2019: 6 · 2018: 6 · 2017: 5 · 2016: 5 · 2015: 4 · 2014: 13 · 2013: 10 · 2012: 7
FWCI: 2.97
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Oncogene (publishedVersion)
PubMed (publishedVersion)
Funders: Deutsche Forschungsgemeinschaft
Topics: Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
Keywords: p53, ribosomal DNA transcription, RNA polymerase I, pre-rRNA synthesis, transcriptional repression, tumor suppressor, growth arrest, mutant p53, p53 knockout mice, rDNA promoter, intergenic spacer, cell proliferation
MeSH terms: Animals, DNA, Ribosomal, RNA Polymerase I, RNA Precursors, Transcription, Genetic, Tumor Suppressor Protein p53, Mice, Knockout, Mice

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p53 represses ribosomal gene transcription

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