ArticleCell death & disease2021
Puma, noxa, p53, and p63 differentially mediate stress pathway induced apoptosis.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 91 citations in OpenAlex.
- Levofloxacin enhances 5-fluorouracil efficacy in colorectal cancer by activating the DDR-TP53-mitochondrial apoptosis axis.iScience · 2026Article
- Evaluation of novel targeted small-molecule therapeutics in desmoplastic small round cell tumor (DSRCT) cells.Journal of cancer research and clinical oncology · 2026Article
- Cell Death Induction by MO2455, a Novel Potential Anti-Cancer Agent in Monocytic and T-Cell Leukemia Cells.Cells · 2026Article
- Deciphering autophagy-metabolism interactions in cancer drug resistance: a comprehensive review.Cancer chemotherapy and pharmacology · 2026Review
- Rapgef1 paralog-mediated regulation of Wnt/β-catenin signaling orchestrates early embryo tissue patterning and morphogenesis.Cell communication and signaling : CCS · 2026Article
- Article
- PUMA-induced apoptosis drives bone marrow failure and genomic instability in telomerase-deficient mice.Cell death and differentiation · 2026Article
- TH-302 (evofosfamide) monotherapy exerts anticancer activity in Ewing's sarcoma cells under hypoxia.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- The multifaceted role of PUMA in cell death pathways: its therapeutic potential across cancer types.Cell communication and signaling : CCS · 2025Review
- NDRG2 upregulation induces astrocytic apoptosis via AKT inhibition and FoxO3a-Puma activation in depression.Communications biology · 2025Article
- Novel p53 reactivators that are synergistic with olaparib for the treatment of gynecologic cancers with mutant p53.Translational oncology · 2025Article
- Reversing the Warburg Effect: YW3-56 Induces Leukemia Differentiation via AKT-Mediated Glucose Metabolic Reprogramming.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Pterostilbene (grape flavonoid) mitigates gastric ulcer events in vivo: biochemical and histopathological approaches.Journal of molecular histology · 2025Article
- The Multifaceted Role of p53 in Cancer Molecular Biology: Insights for Precision Diagnosis and Therapeutic Breakthroughs.Biomolecules · 2025Review
- Deletion of p63 exon 13 in mice reveals C-terminal isoform-specific functions in epithelial development.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Disrupted development of sensory systems and the cerebellum in a zebrafish ebf3a mutant.G3 (Bethesda, Md.) · 2025Article
- Article
- Marine natural product Methyl mycophenolate inhibits gastric cancer growth through regulating p53 and the downstream pathways.Cancer cell international · 2025Article
- Engineering precision zebrafish alleles of human disease.bioRxiv : the preprint server for biology · 2025Article
- Inhibition of ATG5-mediated autophagy maintains PMAIP1 stability to promote cell apoptosis and suppress triple-negative breast cancer progression.Discover oncology · 2025Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Cellular stress can lead to several human disease pathologies due to aberrant cell death. The p53 family (tp53, tp63, and tp73) and downstream transcriptional apoptotic target genes (PUMA/BBC3 and NOXA/PMAIP1) have been implicated as mediators of stress signals. To evaluate the importance of key stress response components in vivo, we have generated zebrafish null alleles in puma, noxa, p53, p63, and p73. Utilizing these genetic mutants, we have deciphered that the apoptotic response to genotoxic stress requires p53 and puma, but not p63, p73, or noxa. We also identified a delayed secondary wave of genotoxic stress-induced apoptosis that is p53/puma independent. Contrary to genotoxic stress, ER stress-induced apoptosis requires p63 and puma, but not p53, p73, or noxa. Lastly, the oxidative stress-induced apoptotic response requires p63, and both noxa and puma. Our data also indicate that while the neural tube is poised for apoptosis due to genotoxic stress, the epidermis is poised for apoptosis due to ER and oxidative stress. These data indicate there are convergent as well as unique molecular pathways involved in the different stress responses. The commonality of puma in these stress pathways, and the lack of gross or tumorigenic phenotypes with puma loss suggest that a inhibitor of Puma may have therapeutic application. In addition, we have also generated a knockout of the negative regulator of p53, mdm2 to further evaluate the p53-induced apoptosis. Our data indicate that the p53 null allele completely rescues the mdm2 null lethality, while the puma null completely rescues the mdm2 null apoptosis but only partially rescues the phenotype. Indicating Puma is the key mediator of p53-dependent apoptosis. Interestingly the p53 homozygous null zebrafish develop tumors faster than the previously described p53 homozygous missense mutant zebrafish, suggesting the missense allele may be hypomorphic allele.
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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.