ArticleOncotarget2016
Loss of p53-mediated cell-cycle arrest, senescence and apoptosis promotes genomic instability and premature aging.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
47 citing papers in PubMed, 84 citations in OpenAlex.
- Oncoviruses at the Crossroads of Ageing and Cancer: Molecular Mechanisms and Key Signalling Pathways.Reviews in medical virology · 2026Review
- Danshensu Ethyl Ester Induces Ferroptosis Through Targeted Inhibition of SLC7A11 Transport Function in NSCLC.Thoracic cancer · 2026Article
- Mechanism and potential therapeutic strategies of genetic abnormalities involved in deoxyribonucleic acid double-strand breaks leading to the development of human non-obstructive azoospermia.Reproductive biology and endocrinology : RB&E · 2026Review
- Ferroptosis-immune crosstalk in ionizing radiation-induced testicular injury: mechanisms and therapeutic opportunities.Frontiers in immunology · 2026Review
- Arsenome, Arsenobolome, and Arsenobiolome.International journal of molecular sciences · 2025Review
- MicroRNAs at the crossroads of exercise and ferroptosis: a regulatory bridge.Clinical and experimental medicine · 2025Review
- ATM and p53 in aging and cancer: a double-edged sword in genomic integrity.Biogerontology · 2025Review
- The metabolites of gut microbiota: their role in ferroptosis in inflammatory bowel disease.European journal of medical research · 2025Review
- The DNA double-strand break repair proteins γH2AX, RAD51, BRCA1, RPA70, KU80, and XRCC4 exhibit follicle-specific expression differences in the postnatal mouse ovaries from early to older ages.Journal of assisted reproduction and genetics · 2024Article
- Differential expression of ferroptosis-related proteins in urinary exosomes: potential indicators for monitoring acute gout attack.Frontiers in molecular biosciences · 2024Article
- Ferroptosis, autophagy, tumor and immunity.Heliyon · 2023Review
- Crosstalk between Wnt/β-catenin signaling pathway and DNA damage response in cancer: a new direction for overcoming therapy resistance.Frontiers in pharmacology · 2023Review
- Mutant p53 in cancer: from molecular mechanism to therapeutic modulation.Cell death & disease · 2022Review
- Reducing the aneuploid cell burden - cell competition and the ribosome connection.Disease models & mechanisms · 2022Review
- Comprehensive analysis of the relationship between the ferroptosis and tumor-infiltrating immune cells, mutation, and immunotherapy in breast cancer.Annals of translational medicine · 2022Article
- Whole-mount Senescence-Associated Beta-Galactosidase (SA-β-GAL) Activity Detection Protocol for Adult Zebrafish.Bio-protocol · 2022Article
- p53 in ferroptosis regulation: the new weapon for the old guardian.Cell death and differentiation · 2022Review
- Deciphering the acetylation code of p53 in transcription regulation and tumor suppression.Oncogene · 2022Review
- 1,25-D3 attenuates cerebral ischemia injury by regulating mitochondrial metabolismFrontiers in aging neuroscience · 2022Article
- Ferroptosis in lymphoma: Emerging mechanisms and a novel therapeutic approach.Frontiers in genetics · 2022Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Although p53-mediated cell cycle arrest, senescence and apoptosis are well accepted as major tumor suppression mechanisms, the loss of these functions does not directly lead to tumorigenesis, suggesting that the precise roles of these canonical activities of p53 need to be redefined. Here, we report that the cells derived from the mutant mice expressing p533KR, an acetylation-defective mutant that fails to induce cell-cycle arrest, senescence and apoptosis, exhibit high levels of aneuploidy upon DNA damage. Moreover, the embryonic lethality caused by the deficiency of XRCC4, a key DNA double strand break repair factor, can be fully rescued in the p533KR/3KR background. Notably, despite high levels of genomic instability, p533KR/3KRXRCC4-/- mice, unlike p53-/- XRCC4-/- mice, are not succumbed to pro-B-cell lymphomas. Nevertheless, p533KR/3KR XRCC4-/- mice display aging-like phenotypes including testicular atrophy, kyphosis, and premature death. Further analyses demonstrate that SLC7A11 is downregulated and that p53-mediated ferroptosis is significantly induced in spleens and testis of p533KR/3KRXRCC4-/- mice. These results demonstrate that the direct role of p53-mediated cell cycle arrest, senescence and apoptosis is to control genomic stability in vivo. Our study not only validates the importance of ferroptosis in p53-mediated tumor suppression in vivo but also reveals that the combination of genomic instability and activation of ferroptosis may promote aging-associated phenotypes.
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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.