ArticleThe EMBO journal2007
Constitutive mTOR activation in TSC mutants sensitizes cells to energy starvation and genomic damage via p53.
Article in The EMBO journal, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers.
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Who cites it
107 citing papers in PubMed, 160 citations in OpenAlex.
- Targeting endoplasmic reticulum export disrupts metabolic resilience in multiple myeloma.Signal transduction and targeted therapy · 2026Article
- Co-treatment of Colchicine and Rosiglitazone synergistically inhibits cytokine-driven inflammation and modulates the related hsa-miRNA26a-5p, hsa-miRNA21-5p, and STAT3 expression in non-small cell lung cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Nucleolus as a cornerstone linking proliferation and metabolism to cellular responses to stress: involvement of transcription factors MYC and p53.Frontiers in molecular biosciences · 2026Review
- Transgenerational inheritance of diminished ovarian reserve triggered by prenatal propylparaben exposure in mice.Nature communications · 2025Article
- Review
- mTORC1 regulates cell survival under glucose starvation through 4EBP1/2-mediated translational reprogramming of fatty acid metabolism.Nature communications · 2024Article
- Activation of mTOR signaling in adult lung microvascular progenitor cells accelerates lung aging.The Journal of clinical investigation · 2023Article
- MicroRNA Expression Profile in TSC Cell Lines and the Impact of mTOR Inhibitor.International journal of molecular sciences · 2022Article
- The complexity of p53-mediated metabolic regulation in tumor suppression.Seminars in cancer biology · 2022Review
- Global cellular response to chemical perturbation of PLK4 activity and abnormal centrosome number.eLife · 2022Article
- Age-Related Lysosomal Dysfunctions.Cells · 2022Review
- Article
- Genome-wide CRISPR screens using isogenic cells reveal vulnerabilities conferred by loss of tumor suppressors.Science advances · 2022Article
- Differential expression of gene co-expression networks related to the mTOR signaling pathway in bipolar disorder.Translational psychiatry · 2022Article
- It's Getting Complicated-A Fresh Look at p53-MDM2-ARF Triangle in Tumorigenesis and Cancer Therapy.Frontiers in cell and developmental biology · 2022Review
- Good Cop, Bad Cop: The Different Roles of SRPKs.Frontiers in genetics · 2022Review
- MicroRNA-34a activation in tuberous sclerosis complex during early brain development may lead to impaired corticogenesis.Neuropathology and applied neurobiology · 2021Article
- Upregulation of the pathogenic transcription factor SPI1/PU.1 in tuberous sclerosis complex and focal cortical dysplasia by oxidative stress.Brain pathology (Zurich, Switzerland) · 2021Article
- Tsc1 regulates tight junction independent of mTORC1.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- FKBP39 controls nutrient dependent Nprl3 expression and TORC1 activity in Drosophila.Cell death & disease · 2021Article
47 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Miscoordination of growth and proliferation with the cellular stress response can lead to tumorigenesis. Mammalian target of rapamycin (mTOR), a central cell growth controller, is highly activated in some malignant neoplasms, and its clinical implications are under extensive investigation. We show that constitutive mTOR activity amplifies p53 activation, in vitro and in vivo, by stimulating p53 translation. Thus, loss of TSC1 or TSC2, the negative regulators of mTOR, results in dramatic accumulation of p53 and apoptosis in response to stress conditions. In other words, the inactivation of mTOR prevents cell death by nutrient stress and genomic damage via p53. Consistently, we also show that p53 is elevated in TSC tumors, which rarely become malignant. The coordinated relationship between mTOR and p53 during cellular stress provides a possible explanation for the benign nature of hamartoma syndromes, including TSC. Clinically, this also suggests that the efficacy of mTOR inhibitors in anti-neoplastic therapy may also depend on p53 status, and mTOR inhibitors may antagonize the effects of genotoxic chemotherapeutics.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.