p53 represses ribosomal gene transcription
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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Induction of p53 leads to downregulation of rRNA genes and of genes that are required for import and export of ribosomal proteins from the nucleus.
“Induction of p53 leads to downregulation of rRNA genes212, 213 and of genes that are required for import and export of ribosomal proteins from the nucleus.214”
From Census and evaluation of p53 target genes (2017) · cites this paper as [212]
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- Authors
- Budde, A., & Grummt, I.
- Affiliations
- German Cancer Research Center (DE)
- ORCID
- Grummt, Ingrid
- Venue
- Oncogene
- Published
- 1999-01-28
- Volume
- 18
- Issue
- 4
- Pages
- 1119-1124
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- 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
- 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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