ArticleCancer biology & therapy2014
mTOR inhibitors blunt the p53 response to nucleolar stress by regulating RPL11 and MDM2 levels.
Article in Cancer biology & therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 31 citations in OpenAlex.
- Tunable Chemical and Optical Modulation of ER-Plasma Membrane Contact-Site Geometry, Dynamics, and Protein Recruitment with High-Fidelity Visualization.Analytical chemistry · 2026Article
- A nucleolar stress gene signature enables quantitative scoring across multi-omics contexts.Communications biology · 2026Article
- Signaling to make human ribosomes: Connections between the cytoplasm and the nucleolus.Molecular cell · 2026Review
- Tunable Chemical and Optical Control of ER-Plasma Membrane Contact Site Geometry and Dynamics with High-Fidelity Visualization.bioRxiv : the preprint server for biology · 2026Article
- Article
- The stress sensor GCN2 differentially controls ribosome biogenesis in colon cancer according to the nutritional context.Molecular oncology · 2024Article
- Interaction of Camptothecin Anticancer Drugs with Ribosomal Proteins L15 and L11: A Molecular Docking Study.Molecules (Basel, Switzerland) · 2023Article
- p53 at the crossroad of DNA replication and ribosome biogenesis stress pathways.Cell death and differentiation · 2022Review
- Epithelial to Mesenchymal Transition Relevant Subtypes with Distinct Prognosis and Responses to Chemo- or Immunotherapies in Osteosarcoma.Journal of immunology research · 2022Article
- Dieckol exerts anticancer activity in human osteosarcoma (MG-63) cells through the inhibition of PI3K/AKT/mTOR signaling pathway.Saudi journal of biological sciences · 2021Article
- EBP2, a novel NPM-ALK-interacting protein in the nucleolus, contributes to the proliferation of ALCL cells by regulating tumor suppressor p53.Molecular oncology · 2021Article
- Estrogen and estrogen receptors chauffeur the sex-biased autophagic action in liver.Cell death and differentiation · 2020Article
- Emerging Role of the Nucleolar Stress Response in Autophagy.Frontiers in cellular neuroscience · 2019Review
- NVP-BEZ235 synergizes cisplatin sensitivity in osteosarcoma.Oncotarget · 2018Article
- Review
- Heterozygous loss of TSC2 alters p53 signaling and human stem cell reprogramming.Human molecular genetics · 2017Article
- New roles for Dicer in the nucleolus and its relevance to cancer.Cell cycle (Georgetown, Tex.) · 2017Review
- Article
- The roles of RRP15 in nucleolar formation, ribosome biogenesis and checkpoint control in human cells.Oncotarget · 2017Article
- mTOR: An attractive therapeutic target for osteosarcoma?Oncotarget · 2016Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mechanistic target of rapamycin (mTOR) is a master regulator of cell growth through its ability to stimulate ribosome biogenesis and mRNA translation. In contrast, the p53 tumor suppressor negatively controls cell growth and is activated by a wide range of insults to the cell. The mTOR and p53 signaling pathways are connected by a number of different mechanisms. Chemotherapeutics that inhibit ribosome biogenesis often induce nucleolar stress and activation of p53. Here we have investigated how the p53 response to nucleolar stress is affected by simultaneous mTOR inhibition in osteosarcoma and glioma cell lines. We found that inhibitors of the mTOR pathway including rapamycin, wortmannin, and caffeine blunted the p53 response to nucleolar stress induced by actinomycin D. Synthetic inhibitors of mTOR (temsirolimus, LY294.002 and PP242) also impaired actinomycin D triggered p53 stabilization and induction of p21. Ribosomal protein (RPL11) is known to be required for p53 protein stabilization following nucleolar stress. Treatment of cells with mTOR inhibitors may lead to reduced synthesis of RPL11 and thereby destabilize p53. We found that rapamycin mimicked the effect of RPL11 depletion in terms of blunting the p53 response to nucleolar stress. However, the extent to which the levels of p53 and RPL11 were reduced by rapamycin varied between cell lines. Additional mechanisms whereby rapamycin blunts the p53 response to nucleolar stress are likely to be involved. Indeed, rapamycin increased the levels of endogenous MDM2 despite inhibition of its phosphorylation at Ser-166. Our findings may have implications for the design of combinatorial cancer treatments with mTOR pathway inhibitors.
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