ArticleOncogene2016
Direct relationship between the level of p53 stabilization induced by rRNA synthesis-inhibiting drugs and the cell ribosome biogenesis rate.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 61 citations in OpenAlex.
- RNA Polymerase III subunit Polr3a is required for craniofacial cartilage and bone development in zebrafish.PLoS genetics · 2026Article
- Establishment of an imaging-based screening pipeline for the identification of human ribosome biogenesis inhibitors.BMC biology · 2025Article
- Downregulation of rRNA synthesis by BCL-2 induces chemoresistance in diffuse large B cell lymphoma.iScience · 2025Article
- The G-quadruplex ligand CX-5461: an innovative candidate for disease treatment.Journal of translational medicine · 2025Review
- SLFN11-mediated ribosome biogenesis impairment induces TP53-independent apoptosis.Molecular cell · 2025Article
- Ribosome biogenesis rate, a parameter of sensitivity to chemotherapeutic drugs inhibiting rRNA synthesis.Oncology reviews · 2025Review
- 9S1R nullomer peptide induces mitochondrial pathology, metabolic suppression, and enhanced immune cell infiltration, in triple-negative breast cancer mouse model.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Article
- Nullomer peptide increases immune cell infiltration and reduces tumor metabolism in triple negative breast cancer mouse model.Research square · 2023Article
- RNA Polymerases I and III in development and disease.Seminars in cell & developmental biology · 2023Review
- Dynamic regulation and requirement for ribosomal RNA transcription during mammalian development.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Nucleolin loss of function leads to aberrant Fibroblast Growth Factor signaling and craniofacial anomalies.Development (Cambridge, England) · 2022Article
- Review
- Single-cell analysis of p53 transitional dynamics unravels stimulus- and cell type-dependent signaling output motifs.BMC biology · 2022Article
- Genes affecting the extension of chronological lifespan in Schizosaccharomyces pombe (fission yeast).Molecular microbiology · 2021Review
- BOP1 Silencing Suppresses Gastric Cancer Proliferation through p53 Modulation.Current medical science · 2021Article
- Review
- The nucleolus: a central response hub for the stressors that drive cancer progression.Cellular and molecular life sciences : CMLS · 2019Review
- The Ribosome Biogenesis-Cancer Connection.Cells · 2019Review
- The nucleolus, an ally, and an enemy of cancer cells.Histochemistry and cell biology · 2018Review
- tp53-dependent and independent signaling underlies the pathogenesis and possible prevention of Acrofacial Dysostosis-Cincinnati type.Human molecular genetics · 2018Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many drugs currently used in chemotherapy work by hindering the process of ribosome biogenesis. In tumors with functional p53, the inhibition of ribosome biogenesis may contribute to the efficacy of this treatment by inducing p53 stabilization. As the level of stabilized p53 is critical for the induction of cytotoxic effects, it seems useful to highlight those cancer cell characteristics that can predict the degree of p53 stabilization following the treatment with inhibitors of ribosome biogenesis. In the present study we exposed a series of p53 wild-type human cancer cell lines to drugs such as actinomycin D (ActD), doxorubicin, 5-fluorouracil and CX-5461, which hinder ribosomal RNA (rRNA) synthesis. We found that the amount of stabilized p53 was directly related to the level of ribosome biogenesis in cells before the drug treatment. This was due to different levels of inactivation of the ribosomal proteins-MDM2 pathway of p53 digestion. Inhibition of rRNA synthesis always caused cell cycle arrest, independent of the ribosome biogenesis rate of the cells, whereas apoptosis occurred only in cells with a high rDNA transcription rate. The level of p53 stabilization induced by drugs acting in different ways from the inhibition of ribosome biogenesis, such as hydroxyurea (HU) and nutlin-3, was independent of the level of ribosome biogenesis in cells and always lower than that occurring after the inhibition of rRNA synthesis. Interestingly, in cells with a low ribosome biogenesis rate, the combined treatment with ActD and HU exerted an additive effect on p53 stabilization. These results indicated that (i) drugs inhibiting ribosome biogenesis may be highly effective in p53 wild-type cancers with a high ribosome biogenesis rate, as they induce apoptotic cell death, and (ii) the combination of drugs capable of stabilizing p53 through different mechanisms may be useful for treating cancers with a low ribosome biogenesis rate.
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