ArticleCell death & disease2019
Inhibition of DYRK1A-EGFR axis by p53-MDM2 cascade mediates the induction of cellular senescence.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 38 citations in OpenAlex.
- Article
- Review
- From EGFR PTM network to TKI resistance: spatial subtypes and targeting in lung cancer.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- Hepatitis B Virus X Protein Induces Reactive Oxygen Species Generation via Activation of p53 in Human Hepatoma Cells.Biomolecules · 2024Article
- Elimination of radiation-induced senescent cancer cells and stromal cells in vitro by near-infrared photoimmunotherapy.Cancer medicine · 2024Article
- MDM4 was associated with poor prognosis and tumor-immune infiltration of cancers.European journal of medical research · 2024Article
- The potential for senotherapy as a novel approach to extend life quality in veterinary medicine.Frontiers in veterinary science · 2024Review
- Dasatinib Plus Quercetin Alleviates Choroid Neovascularization by Reducing the Cellular Senescence Burden in the RPE-Choroid.Investigative ophthalmology & visual science · 2023Article
- Aging microenvironment and antitumor immunity for geriatric oncology: the landscape and future implications.Journal of hematology & oncology · 2023Review
- Single-cell profiling of mouse and primate ovaries identifies high levels ofMolecular therapy. Nucleic acids · 2023Article
- Selective Macrocyclic Inhibitors of DYRK1A/B.ACS medicinal chemistry letters · 2022Article
- The chromosome 21 kinase DYRK1A: emerging roles in cancer biology and potential as a therapeutic target.Oncogene · 2022Review
- Targeting DYRK1A/B kinases to modulate p21-cyclin D1-p27 signalling and induce anti-tumour activity in a model of human glioblastoma.Journal of cellular and molecular medicine · 2021Article
- Diabetic Kinome Inhibitors-A New Opportunity for β-Cells Restoration.International journal of molecular sciences · 2021Review
- Identification of harmine and β-carboline analogs from a high-throughput screen of an approved drug collection; profiling as differential inhibitors of DYRK1A and monoamine oxidase A and for in vitro and in vivo anti-cancer studies.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2021Article
- RECQL4 regulates DNA damage response and redox homeostasis in esophageal cancer.Cancer biology & medicine · 2021Article
- Senolytic Drugs: Reducing Senescent Cell Viability to Extend Health Span.Annual review of pharmacology and toxicology · 2021Review
- DYRK1A: a down syndrome-related dual protein kinase with a versatile role in tumorigenesis.Cellular and molecular life sciences : CMLS · 2021Review
- Targeting Senescent Cells for a Healthier Aging: Challenges and Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2020Review
- Senolytic drugs: from discovery to translation.Journal of internal medicine · 2020Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of p53 may induce apoptosis or cellular senescence in stressed cells. We here report that epidermal growth factor receptor (EGFR) is downregulated by p53 activation in a subset of cancer cell lines, and this EGFR downregulation mediates cellular senescence caused by p53 activation. EGFR confers resistance to senescence by sustaining the ERK signaling. DYRK1A (dual-specificity tyrosine-phosphorylated and tyrosine-regulated kinase 1A), an EGFR-stabilizing kinase, is downregulated by p53 and, when ectopically expressed, can attenuate p53 activation-induced EGFR reduction and cellular senescence. We further showed that the increased degradation of DYRK1A caused by p53 activation was mediated by MDM2. MDM2 was found to physically interact with and ubiquitinate DYRK1A, ultimately leading to its proteosomal degradation. Importantly, administration of Nutlin-3a, which disrupts the binding of MDM2 to p53, but not that of MDM2 to DYRK1A, reduced the levels of DYRK1A and EGFR, induced senescence, and inhibited growth of tumor xenografts formed by U87 glioblastoma cells. Ectopic expression of EGFR in tumor xenografts attenuated senescence and tumor reduction caused by Nultin-3a. Our findings thus established a novel link between p53 and EGFR and may have implications in p53 activation-based therapies.
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