ArticleThe Journal of clinical investigation2017
Dysfunction of the MDM2/p53 axis is linked to premature aging.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- Comprehensive Meta-Analysis on the Impact of theCurrent pharmaceutical design · 2026Pooled it
- Predicting and finding geroprotective compounds through modulating conserved longevity-associated aging modules.Science advances · 2026Article
- Mutant p53 protein accumulation is selectively targetable by proximity-inducing drugs.Nature chemical biology · 2026Article
- Article
- A manually curated gene-phenotype catalogue for progeroid syndromes and premature aging.Aging · 2026Article
- Recessive variants in WSB2 encoding a substrate receptor of E3 ubiquitin ligase underlie a neurodevelopmental syndrome.European journal of human genetics : EJHG · 2026Article
- Progress in the study of the role of C5a-induced tubular cell senescence in the progression of diabetic kidney disease.Annals of medicine · 2025Review
- Design principles of gene circuits for longevity.Trends in cell biology · 2025Review
- Rare phenotypes of white coat color in Simmental calves: genetic causes of syndromic forms of albinism and depigmentation.Molecular genetics and genomics : MGG · 2025Article
- Identification of replicative aging and inflammatory aging signatures via whole-genome CRISPRi screens.Genome biology · 2025Article
- DNA-binding affinity and specificity determine the phenotypic diversity in BCL11B-related disorders.American journal of human genetics · 2025Article
- MDM2 inhibitor induces apoptosis in colon cancer cells through activation of the CHOP-DR5 pathway, independent of p53 phenotype.Frontiers in pharmacology · 2025Article
- Matrine promotes colorectal cancer apoptosis by downregulating shank-associated RH domain interactor expression.World journal of gastrointestinal oncology · 2024Article
- Caspase 5 depletion is linked to hyper-inflammatory response and progeroid syndrome.GeroScience · 2024Article
- USP13 regulates cell senescence through mediating MDM2 stability.Life sciences · 2023Article
- p53 in the Molecular Circuitry of Bone Marrow Failure Syndromes.International journal of molecular sciences · 2023Review
- Tissue specificity and spatio-temporal dynamics of the p53 transcriptional program.Cell death and differentiation · 2023Review
- Multifaceted role for p53 in pancreatic cancer suppression.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Premature ovarian insufficiency: a review on the role of oxidative stress and the application of antioxidants.Frontiers in endocrinology · 2023Review
- Nicotinic acid supplementation contributes to the amelioration of Alzheimer's disease in mouse models.Annals of translational medicine · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 10 institutions in 5 countries.
Funding
Abstract
The tumor suppressor p53, a master regulator of the cellular response to stress, is tightly regulated by the E3 ubiquitin ligase MDM2 via an autoregulatory feedback loop. In addition to its well-established role in tumorigenesis, p53 has also been associated with aging in mice. Several mouse models with aberrantly increased p53 activity display signs of premature aging. However, the relationship between dysfunction of the MDM2/p53 axis and human aging remains elusive. Here, we have identified an antiterminating homozygous germline mutation in MDM2 in a patient affected by a segmental progeroid syndrome. We show that this mutation abrogates MDM2 activity, thereby resulting in enhanced levels and stability of p53. Analysis of the patient's primary cells, genome-edited cells, and in vitro and in vivo analyses confirmed the MDM2 mutation's aberrant regulation of p53 activity. Functional data from a zebrafish model further demonstrated that mutant Mdm2 was unable to rescue a p53-induced apoptotic phenotype. Altogether, our findings indicate that mutant MDM2 is a likely driver of the observed segmental form of progeria.
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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.