ArticleOncogene2019
mTOR kinase leads to PTEN-loss-induced cellular senescence by phosphorylating p53.
Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
97 citing papers in PubMed, 163 citations in OpenAlex.
- LINP1 suppresses radiation-induced cellular senescence in keratinocytes by modulating the mTOR-p53 axis.Molecular and cellular biochemistry · 2026Article
- Review
- Synthesis andACS omega · 2026Article
- Targeting Dental Pulp Stem Cell Senescence: A Potential Strategy for Improving Regenerative Endodontic Procedures.Bioengineering (Basel, Switzerland) · 2026Article
- Exploiting cellular senescence in hematologic malignancies.Translational oncology · 2026Review
- Biobank of genetically defined murine prostate cancer tumoroids uncovers oncogenic pathways and drug vulnerabilities driven by PTEN-loss.Cell reports methods · 2026Article
- The Role of Cellular Senescence in Obstructive Airway Diseases: From Mechanisms to Therapeutic Targets.International journal of molecular sciences · 2026Review
- Harnessing Natural Extracellular Vesicles to Combat Age-Related Diseases: From Aging Drivers to Therapeutic Opportunities.International journal of nanomedicine · 2026Review
- Biomarkers for Recurrence and Prognosis in Metastatic Urothelial Cancer: Emerging Clinical Applications.Journal of Cancer · 2026Review
- Polyploidy and Senescence of Cancer Cells: Impact of Cell Fusion.Advances in experimental medicine and biology · 2026Review
- mTOR signaling networks: mechanistic insights and translational frontiers in disease therapeutics.Signal transduction and targeted therapy · 2025Review
- Integrating Senescence and Oxidative Stress in Cardiac Disease.International journal of molecular sciences · 2025Review
- Aging and lung diseases: Unraveling mechanisms and therapeutic targets.Chinese medical journal pulmonary and critical care medicine · 2025Review
- Targeting the akt/mtor signaling pathway by maprotiline leads to tumor suppression in T-cell lymphoma.Annals of hematology · 2025Article
- Pooled CRISPR screens identifies key regulators of bovine stem cell expansion for cultured meat.Communications biology · 2025Article
- Mutations in tumor signaling, metastases, and synthetic lethality establish distinct patterns.PLoS computational biology · 2025Article
- Review
- Circadian rhythm and aryl hydrocarbon receptor crosstalk in bone marrow adipose tissue and implications in leukemia.Scientific reports · 2025Article
- Senescence in the ageing skin: a new focus on mTORC1 and the lysosome.The FEBS journal · 2025Review
- Harnessing p53 for targeted cancer therapy: new advances and future directions.Transcription · 2025Review
37 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Loss of PTEN, the major negative regulator of the PI3K/AKT pathway induces a cellular senescence as a failsafe mechanism to defend against tumorigenesis, which is called PTEN-loss-induced cellular senescence (PICS). Although many studies have indicated that the mTOR pathway plays a critical role in cellular senescence, the exact functions of mTORC1 and mTORC2 in PICS are not well understood. In this study, we show that mTOR acts as a critical relay molecule downstream of PI3K/AKT and upstream of p53 in PICS. We found that PTEN depletion induces cellular senescence via p53-p21 signaling without triggering DNA damage response. mTOR kinase, a major component of mTORC1 and mTORC2, directly binds p53 and phosphorylates it at serine 15. mTORC1 and mTORC2 compete with MDM2 and increase the stability of p53 to induce cellular senescence via accumulation of the cell cycle inhibitor, p21. In embryonic fibroblasts of PTEN-knockout mice, PTEN deficiency also induces mTORC1 and mTORC2 to bind to p53 instead of MDM2, leading to cellular senescence. These results collectively demonstrate for the first time that mTOR plays a critical role in switching cells from proliferation signaling to senescence signaling via a direct link between the growth-promoting activity of AKT and the growth-suppressing activity of p53.
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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.