ArticleCell death and differentiation2014
ROS-dependent activation of JNK converts p53 into an efficient inhibitor of oncogenes leading to robust apoptosis.
Article in Cell death and differentiation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
132 citing papers in PubMed, 229 citations in OpenAlex.
- Osimertinib Resistance in EGFR-Mutated Non-Small Cell Lung Cancer: Mechanisms and Therapeutic Strategies.MedComm · 2026Review
- Systemic Inflammation Triggers Motor Axon Degeneration Via Macrophage IL-1β-Mediated P53/SIRT1/Autophagy Pathway.Inflammation · 2026Article
- Context‑dependent targeting of thioredoxin reductase 1 in cancer: a mechanistic review.Magyar onkologia · 2026Review
- b-AP15 enhances TRAIL-induced cell death in HNSCC via the induction of ROS/JNK/DR5 signalling.Cancer gene therapy · 2026Article
- Molecular Networks of Redox Dysregulation in Fetal Alcohol Spectrum Disorders: Mechanisms and Therapeutic Prospects.Antioxidants (Basel, Switzerland) · 2026Review
- Potential Mechanisms of MAP Kinase JNK's Involvement in Modulating Cancer Cell Fate in a Cisplatin Concentration-Dependent Manner.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Revisiting ROS: duality in organ aging progression.Molecular biology reports · 2025Review
- Impact of reactive oxygen species on bone regeneration in diabetes: Mechanisms and therapeutic strategies.Redox biology · 2025Review
- Acrylamide-Induced Neuroendocrine Disruption in Adult Male Zebrafish (Danio rerio): Mechanistic Insights into Locomotor, Neuronal, and Reproductive Impairments.Molecular neurobiology · 2025Article
- Garcinol as an Epigenetic Modulator: Mechanisms of Anti-Cancer Activity and Therapeutic Potential.International journal of molecular sciences · 2025Review
- Oxidative Stress Disrupts Gill Function inAntioxidants (Basel, Switzerland) · 2025Article
- Quinazolinedione Derivatives as Potential Anticancer Agents Through Apoptosis Induction in MCF-7.International journal of molecular sciences · 2025Article
- Static magnetic field promotes the doxorubicin toxicity effects on osteosarcoma cells.Scientific reports · 2025Article
- Deciphering UBE4B phosphorylation dynamics: a key mechanism in p53 accumulation and cancer cell response to DNA damage.Cell death discovery · 2025Article
- Female reproductive capacity preservation: antioxidant strategies in combating ovarian aging and cryopreservation challenges.Frontiers in endocrinology · 2025Review
- Mechanisms of the JNK/p38 MAPK signaling pathway in drug resistance in ovarian cancer.Frontiers in oncology · 2025Review
- RGD-Modified Gold Nanoparticles Loaded with SAHA Remodel the Hypoxic Inflammatory Microenvironment via Inhibiting HIF-1α-VEGF Signaling to Enhance Radiosensitivity in NSCLC.International journal of nanomedicine · 2025Article
- Oxidative cell death in cancer: mechanisms and therapeutic opportunities.Cell death & disease · 2024Review
- Identification of a novel form of caspase-independent cell death triggered by BH3-mimetics in diffuse large B-cell lymphoma cell lines.Cell death & disease · 2024Article
- Oxidative Stress and Chronic Myeloid Leukemia: A Balance between ROS-Mediated Pro- and Anti-Apoptotic Effects of Tyrosine Kinase Inhibitors.Antioxidants (Basel, Switzerland) · 2024Review
72 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
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rescue of the p53 tumor suppressor is an attractive cancer therapy approach. However, pharmacologically activated p53 can induce diverse responses ranging from cell death to growth arrest and DNA repair, which limits the efficient application of p53-reactivating drugs in clinic. Elucidation of the molecular mechanisms defining the biological outcome upon p53 activation remains a grand challenge in the p53 field. Here, we report that concurrent pharmacological activation of p53 and inhibition of thioredoxin reductase followed by generation of reactive oxygen species (ROS), result in the synthetic lethality in cancer cells. ROS promote the activation of c-Jun N-terminal kinase (JNK) and DNA damage response, which establishes a positive feedback loop with p53. This converts the p53-induced growth arrest/senescence to apoptosis. We identified several survival oncogenes inhibited by p53 in JNK-dependent manner, including Mcl1, PI3K, eIF4E, as well as p53 inhibitors Wip1 and MdmX. Further, we show that Wip1 is one of the crucial executors downstream of JNK whose ablation confers the enhanced and sustained p53 transcriptional response contributing to cell death. Our study provides novel insights for manipulating p53 response in a controlled way. Further, our results may enable new pharmacological strategy to exploit abnormally high ROS level, often linked with higher aggressiveness in cancer, to selectively kill cancer cells upon pharmacological reactivation of p53.
Indexed as
Identifiers
What OpenQuestion holds
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.