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Repression of RNA Polymerase I Transcription by the Tumor Suppressor p53
Open accessAbstract
The tumor suppressor protein p53 is frequently inactivated in tumors. It functions as a transcriptional activator as well as a repressor for a number of viral and cellular promoters transcribed by RNA polymerase II (Pol II) and by RNA Pol III. Moreover, it appears that p53 also suppresses RNA Pol I transcription. In this study, we examined the molecular mechanism of Pol I transcriptional inhibition by p53. We show that wild-type, but not mutant, p53 can repress Pol I transcription from a human rRNA gene promoter in cotransfection assays. Furthermore, we show that recombinant p53 inhibits rRNA transcription in a cell-free transcription system. In agreement with these results, p53-null epithelial cells display an increased Pol I transcriptional activity compared to that of epithelial cells that express p53. However, both cell lines display comparable Pol I factor protein levels. Our biochemical analysis shows that p53 prevents the interaction between SL1 and UBF. Protein-protein interaction assays indicate that p53 binds to SL1, and this interaction is mostly mediated by direct contacts with TATA-binding protein and TAF(I)110. Moreover, template commitment assays show that while the formation of a UBF-SL1 complex can partially relieve the inhibition of transcription, only the assembly of a UBF-SL1-Pol I initiation complex on the rDNA promoter confers substantial protection against p53 inhibition. In summary, our results suggest that p53 represses RNA Pol I transcription by directly interfering with the assembly of a productive transcriptional machinery on the rRNA promoter.
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“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 [213]
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Metadata
- Authors
- Zhai, W., & Comai, L.
- Affiliations
- University of Southern California (US)
- Corresponding author
- Comai, Lucio
- ORCID
- Comai, Lucio
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2000-08
- Volume
- 20
- Issue
- 16
- Pages
- 5930-5938
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC86070
- OpenAlex
- W2146842824
- Cited by
- 289
- References
- 53
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 8 · 2023: 9 · 2022: 10 · 2021: 14 · 2020: 7 · 2019: 14 · 2018: 13 · 2017: 13 · 2016: 6 · 2015: 14 · 2014: 24 · 2013: 21 · 2012: 7
- FWCI
- 2.53
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM053949, R01 GM53949)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Keywords
- p53, RNA polymerase I transcription, transcriptional repression, UBF, TATA-binding protein, protein-protein interaction, transcription initiation complex, tumor suppressor
- MeSH terms
- HeLa Cells, Humans, Plasmids, RNA Polymerase I, Transcription, Genetic, Transfection, Genes, Tumor Suppressor, Genes, p53, Tumor Suppressor Protein p53
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