ArticleCell death and differentiation2017
Post-translational regulation of p53 function through 20S proteasome-mediated cleavage.
Article in Cell death and differentiation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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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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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
30 citing papers in PubMed, 49 citations in OpenAlex.
- Identification and validation of prognostic genes associated with integrative stress response in lung adenocarcinoma and construction of the risk models.Scientific reports · 2026Article
- A Quantitative High-Throughput Screen Identifies Compounds that Upregulate the p53 Isoform Δ133p53α and Inhibit Cellular Senescence.ACS pharmacology & translational science · 2025Article
- Tracking proteasome degradation: A cross-organ analysis via intact degradomics mass spectrometry.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- p53 Genetics and Biology in Lung Carcinomas: Insights, Implications and Clinical Applications.Biomedicines · 2024Review
- Systematic identification of 20S proteasome substrates.Molecular systems biology · 2024Article
- Mechanisms of ubiquitin-independent proteasomal degradation and their roles in age-related neurodegenerative disease.Frontiers in cell and developmental biology · 2024Review
- p53 isoform expression promotes a stemness phenotype and inhibits doxorubicin sensitivity in breast cancer.Cell death & disease · 2023Article
- p53 Dysregulation in Breast Cancer: Insights on Mutations in theInternational journal of molecular sciences · 2023Article
- The ubiquitin-like modifier FAT10 is degraded by the 20S proteasome in vitro but not in cellulo.Life science alliance · 2023Article
- Allosteric regulation of the 20S proteasome by the Catalytic Core Regulators (CCRs) family.Nature communications · 2023Article
- Review
- Cytoplasmic p53β Isoforms Are Associated with Worse Disease-Free Survival in Breast Cancer.International journal of molecular sciences · 2022Article
- Adaptive homeostasis and the p53 isoform network.EMBO reports · 2021Review
- Cell communication and protein degradation: All in one parasitic package.Journal of extracellular vesicles · 2021Article
- Review
- 20S proteasomes secreted by the malaria parasite promote its growth.Nature communications · 2021Article
- p53 EnhancesInternational journal of molecular sciences · 2020Article
- Review
- The role of MDM2-p53 axis dysfunction in the hepatocellular carcinoma transformation.Cell death discovery · 2020Review
- The Emerging Landscape of p53 Isoforms in Physiology, Cancer and Degenerative Diseases.International journal of molecular sciences · 2019Review
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
The tumor suppressor p53 is a transcription factor that regulates the expression of a range of target genes in response to cellular stress. Adding to the complexity of understanding its cellular function is that in addition to the full-length protein, several p53 isoforms are produced in humans, harboring diverse expression patterns and functionalities. One isoform, Δ40p53, which lacks the first transactivation domain including the binding region for the negative regulator MDM2, was shown to be a product of alternative translation initiation. Here we report the discovery of an alternative cellular mechanism for Δ40p53 formation. We show that the 20S proteasome specifically cleaves the full-length protein (FLp53) to generate the Δ40p53 isoform. Moreover, we demonstrate that a dimer of FLp53 interacts with a Δ40p53 dimer, creating a functional hetero-tetramer. Consequently, the co-expression of both isoforms attenuates the transcriptional activity of FLp53 in a dominant negative manner. Finally, we demonstrate that following oxidative stress, at the time when the 20S proteasome becomes the major degradation machinery and FLp53 is activated, the formation of Δ40p53 is enhanced, creating a negative feedback loop that balances FLp53 activation. Overall, our results suggest that Δ40p53 can be generated by a 20S proteasome-mediated post-translational mechanism so as to control p53 function. More generally, the discovery of a specific cleavage function for the 20S proteasome may represent a more general cellular regulatory mechanism to produce proteins with distinct functional properties.
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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.