ArticleOncogene2000
The loss of mdm2 induces p53-mediated apoptosis.
Article in Oncogene, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 141 citations in OpenAlex.
- The expanding MDM2 universe.Cell death and differentiation · 2026Article
- Elucidating the transcriptomic response of adult-derived mHypoA-2/12 mouse hypothalamic neuron cell line to cannabidiol (CBD) exposure.Journal of applied genetics · 2025Article
- Comparative mathematical modeling reveals the differential effects of high-fat diet and ketogenic diet on the PI3K-Akt signaling pathway in heart.Nutrition & metabolism · 2024Article
- Unlocking the Gateway: The Spatio-Temporal Dynamics of the p53 Family Driven by the Nuclear Pores and Its Implication for the Therapeutic Approach in Cancer.International journal of molecular sciences · 2024Review
- Review
- Activating transcription factor 3 mediates apoptotic functions through a p53-independent pathway in human papillomavirus 18 infected HeLa cells.Virus genes · 2022Article
- Cardiomyocyte-produced miR-339-5p mediates pathology in Duchenne muscular dystrophy cardiomyopathy.Human molecular genetics · 2021Article
- Developmental Acquisition ofGenes · 2021Review
- Regulation of p53 by E3s.Cancers · 2021Review
- Effects of triclosan on antioxidant- and apoptosis-related genes expression in the gill and ovary of zebrafish.Experimental animals · 2020Article
- Drug Development Targeting the Ubiquitin-Proteasome System (UPS) for the Treatment of Human Cancers.Cancers · 2020Review
- The Roles of Ubiquitination Factor E4B (UBE4B) in the Postoperative Prognosis of Patients with Renal Cell Carcinoma and in Renal Tumor Cells Growth and Metastasis.OncoTargets and therapy · 2020Article
- Transcriptome Analysis of Ochratoxin A-Induced Apoptosis in Differentiated Caco-2 Cells.Toxins · 2019Article
- The Effect of Bacterial Peptide p28 on Viability and Apoptosis Status of P53-null HeLa Cells.Advanced pharmaceutical bulletin · 2019Article
- Review
- Alterations in expression levels of genes in p53-related pathways determined using RNA-Seq analysis in patients with breast cancer following CIK therapy.Oncology letters · 2017Article
- The Transactivation Domains of the p53 Protein.Cold Spring Harbor perspectives in medicine · 2017Review
- Cardiac-specific ablation of the E3 ubiquitin ligase Mdm2 leads to oxidative stress, broad mitochondrial deficiency and early death.PloS one · 2017Article
- Regulation of the Mdm2-p53 signaling axis in the DNA damage response and tumorigenesis.Translational cancer research · 2016Article
- The p53-Mdm2 interaction and the E3 ligase activity of Mdm2/Mdm4 are conserved from lampreys to humans.Genes & development · 2016Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
The p53 tumor suppressor gene product is negatively regulated by the product of its downstream target, mdm2. The deletion of mdm2 in the mouse results in embryonic lethality at 5.5 days post coitum (d.p.c.) which can be overcome by simultaneous loss of the p53 tumor suppressor, substantiating the importance of the negative regulatory function of MDM2 on p53 function in vivo. Hence, the loss of MDM2 allowed the unregulated p53 protein to continuously exert its growth-suppressing activity, which either led to a complete G1 arrest or induced the p53-dependent apoptotic pathway, resulting in the death of the mdm2-/- embryos. To determine which of these possibilities is occurring, mouse embryo fibroblasts (MEFs) from p53 null and p53/mdm2 double null embryos were transfected with a retroviral vector carrying a temperature-sensitive p53 (tsp53) cDNA. Shifting of single-cell clonal populations to the permissive temperature caused the p53-/-mdm2-/- fibroblasts expressing tsp53 to undergo apoptosis in a dose-dependent manner. This phenotype was not observed in the tsp53 expressing p53-/- clones nor the parental cell lines. Thus, our data indicate that the simple loss of mdm2 can induce the p53-dependent apoptotic pathway in vivo.
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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.