ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2004
p53 activation domain 1 is essential for PUMA upregulation and p53-mediated neuronal cell death.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 92 citations in OpenAlex.
- Exploring NMDAR pathways in ischemic stroke: implications for neurotoxic and neuroprotective mechanisms and therapeutic strategies.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Molecular mechanisms of programmed cell death and potential targeted pharmacotherapy in ischemic stroke (Review).International journal of molecular medicine · 2025Review
- Neurotoxic Effect of Myricitrin in Copper-Induced Oxidative Stress Is Mediated by Increased Intracellular CaAntioxidants (Basel, Switzerland) · 2025Article
- Signaling pathways involved in ischemic stroke: molecular mechanisms and therapeutic interventions.Signal transduction and targeted therapy · 2022Review
- Polyglutamine Expansion in Huntingtin and Mechanism of DNA Damage Repair Defects in Huntington's Disease.Frontiers in cellular neuroscience · 2022Review
- Autophagy and apoptosis cascade: which is more prominent in neuronal death?Cellular and molecular life sciences : CMLS · 2021Review
- Transcriptomic Changes Associated with Loss of Cell Viability Induced by Oxysterol Treatment of a Retinal Photoreceptor-Derived Cell Line: An In Vitro Model of Smith-Lemli-Opitz Syndrome.International journal of molecular sciences · 2021Article
- Cell Death Pathways in Ischemic Stroke and Targeted Pharmacotherapy.Translational stroke research · 2020Review
- Systems biology analysis identifies molecular determinants of chemotherapy-induced diarrhoea.Journal of molecular medicine (Berlin, Germany) · 2020Article
- Article
- Apoptotic cell death regulation in neurons.The FEBS journal · 2019Review
- Role of PUMA in the methamphetamine-induced migration of microglia.Metabolic brain disease · 2019Article
- Inhibiting aberrant p53-PUMA feedback loop activation attenuates ischaemia reperfusion-induced neuroapoptosis and neuroinflammation in rats by downregulating caspase 3 and the NF-κB cytokine pathway.Journal of neuroinflammation · 2018Article
- Post-traumatic administration of the p53 inactivator pifithrin-α oxygen analogue reduces hippocampal neuronal loss and improves cognitive deficits after experimental traumatic brain injury.Neurobiology of disease · 2016Article
- Organotypic Spinal Cord Culture: a Proper Platform for the Functional Screening.Molecular neurobiology · 2016Review
- Thymosin beta 4 up-regulates miR-200a expression and induces differentiation and survival of rat brain progenitor cells.Journal of neurochemistry · 2016Article
- Inactivation of PNKP by mutant ATXN3 triggers apoptosis by activating the DNA damage-response pathway in SCA3.PLoS genetics · 2015Article
- p53 and mitochondrial function in neurons.Biochimica et biophysica acta · 2014Review
- Role of metabotropic glutamate receptor 5 signaling and homer in oxygen glucose deprivation-mediated astrocyte apoptosis.Molecular brain · 2013Article
- Pifithrin-α enhances the survival of transplanted neural stem cells in stroke rats by inhibiting p53 nuclear translocation.CNS neuroscience & therapeutics · 2013Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The p53 tumor suppressor gene has been implicated in the regulation of apoptosis in a number of different neuronal death paradigms. Because of the importance of p53 in neuronal injury, we questioned the mechanism underlying p53-mediated apoptosis in neurons. Using adenoviral-mediated gene delivery, reconstitution experiments, and mice carrying a knock-in mutation in the endogenous p53 gene, we show that the transactivation function of p53 is essential to induce neuronal cell death. Although p53 possesses two transactivation domains that can activate p53 targets independently, we demonstrate that the first activation domain (ADI) is required to drive apoptosis after neuronal injury. Furthermore, the BH3-only proteins Noxa and PUMA exhibit differential regulation by the two transactivation domains. Here, we show that Noxa can be induced by either activation domain, whereas PUMA induction requires both activation domains to be intact. Unlike Noxa, the upregulation of PUMA alone is sufficient to induce neuronal cell death. We demonstrate, therefore, that the first transactivation domain of p53 is indispensable for the induction of neuronal cell death.
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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.