ArticleCell death and differentiation2013
A threshold mechanism mediates p53 cell fate decision between growth arrest and apoptosis.
Article in Cell death and differentiation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 145 papers, 1 of them a synthesis that pooled it.
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.
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Who cites it
145 citing papers in PubMed, 1 synthesis or guideline pooled it, 265 citations in OpenAlex.
- Integration of TP53, DREAM, MMB-FOXM1 and RB-E2F target gene analyses identifies cell cycle gene regulatory networks.Nucleic acids research · 2016Pooled it
- MAPK signaling cascades mediate distinct glucocorticoid resistance mechanisms in pediatric leukemia.Blood · 2015Trial
- Central nervous system involvement in acute lymphoblastic leukemia: pathogenesis and targeted therapy.Leukemia · 2026Review
- Thymoquinone and pentoxifylline modulate 5-fluorouracil-induced senescence and apoptosis in colorectal cancer spheroids.Research in pharmaceutical sciences · 2026Article
- The Enigmatic Tumor Suppressor p53 Biomolecule: Its Role and Prognostic and Predictive Values in Cancer Therapy and Precision Medicine.Biomolecules · 2026Review
- Memory impairment and chronic high-dose Δ9-THC/cannabis exposure: a narrative review of molecular mechanisms underlying neurotoxic effects.Psychopharmacology · 2026Review
- Article
- CHK1 and CHK2 as Context-Dependent Rheostats of Genotoxic Stress: Implications for Cell Fate and Tumor Immunity.International journal of biological sciences · 2026Review
- Pharmacological activation of p53 induces dose-dependent changes in endothelial cell fate during angiogenic sprouting.Cell death & disease · 2025Article
- What Is Apoptosis and Why Is It Inhibited by the Most Important Tumor Suppressor (p53)?International journal of molecular sciences · 2025Review
- Interrogating the regulatory epigenome of cellular senescence.Cellular and molecular life sciences : CMLS · 2025Review
- Leveraging chromatin packing domains to target chemoevasion in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- p53 and TIGAR promote redox control to protect against metabolic dysfunction-associated steatohepatitis.JHEP reports : innovation in hepatology · 2025Article
- Article
- Post-transplant G-CSF impedes engraftment of gene-edited human hematopoietic stem cells by exacerbating p53-mediated DNA damage response.Cell stem cell · 2025Article
- Deubiquitinating enzymes: Key regulators of ferroptosis and pyroptosis and novel targets for cancer intervention.International journal of biological sciences · 2025Review
- The mitochondrial enzyme pyruvate carboxylase restricts pancreatic β-cell senescence by blocking p53 activation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Determinants of p53 DNA binding, gene regulation, and cell fate decisions.Cell death and differentiation · 2024Review
- MDM2/MDMX inhibition by Sulanemadlin synergizes with anti-Programmed Death 1 immunotherapy in wild-type p53 tumors.iScience · 2024Article
- A stochastic vs deterministic perspective on the timing of cellular events.Nature communications · 2024Article
85 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The p53 tumor suppressor responds to certain cellular stresses by inducing transcriptional programs that can lead to growth arrest or apoptosis. However, the molecular mechanisms responsible for choosing between these two cell fates are not well understood. Previous studies have suggested that p53 selectively activates proarrest target genes, due to the higher affinity of p53 for their promoters compared with proapoptotic genes. Here we show using microarray and chromatin immunoprecipitation that p53 binds to and transcriptionally activates both its proarrest and proapoptotic target genes proportionally to induced p53 expression levels. Further, we provide evidence that to trigger apoptosis, cells must overcome an apoptotic threshold, whose height is determined by expression levels of p53 and its targets, the duration of their expression and the cellular context. We demonstrate in multiple cells lines that below this threshold, expression levels of p53 and its targets were sufficient to induce arrest but not apoptosis. Above this threshold, p53 and its targets triggered extensive apoptosis. Moreover, lowering this threshold with inhibitors of antiapoptotic Bcl-2 family proteins sensitized cells to p53-induced apoptosis. These findings argue that agents that lower the apoptotic threshold should increase the efficacy of p53-mediated cancer therapy.
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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.