ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
DAPK1-p53 interaction converges necrotic and apoptotic pathways of ischemic neuronal death.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.
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Who cites it
67 citing papers in PubMed, 1 synthesis or guideline pooled it, 118 citations in OpenAlex.
- Cationic Arginine-Rich Peptides (CARPs): A Novel Class of Neuroprotective Agents With a Multimodal Mechanism of Action.Frontiers in neurology · 2020Pooled it
- Protein-protein interaction-mediated signaling networks in ischemic stroke: from molecular mechanisms to therapeutic strategies.Acta pharmacologica Sinica · 2026Review
- Crosstalk between death-associated protein kinase 1-regulated mechanisms and dysfunctions in alzheimer's disease.Molecular biology reports · 2026Review
- Neuroglia and immune cells play different roles in neuroinflammation and neuroimmune response in post-stroke neural injury and repair.Acta pharmacologica Sinica · 2026Review
- A Novel PROTAC Confers a Dual Benefit Against Amyloid and Tau Pathology in Alzheimer's Disease via DAPK1 Degradation.International journal of biological sciences · 2026Article
- DAPK1-positve macrophages facilitate immunosuppressive microenvironment and determine immunotherapy efficacy in colorectal cancer.Journal of translational medicine · 2025Article
- Epigenetic Regulation of DAPK1 and Netrin-1 Drives Diabetic Encephalopathy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Targeted reactivation of the novel tumor suppressor DAPK1, an upstream regulator of p53, in high-grade serous ovarian cancer by mRNA liposomes reduces viability and enhances drug sensitivity in preclinical models.Cancer communications (London, England) · 2025Article
- p53-regulated non-apoptotic cell death pathways and their relevance in cancer and other diseases.Nature reviews. Molecular cell biology · 2025Review
- Article
- Protein kinases in neurodegenerative diseases: current understandings and implications for drug discovery.Signal transduction and targeted therapy · 2025Review
- Death-associated protein kinase 1: a double-edged sword in health and disease.Frontiers in immunology · 2025Review
- Article
- Quantitative Proteomic and Phosphoproteomic Analyses Reveal a Role of Death-Associated Protein Kinase 1 in Regulating Hippocampal Synapse.Molecular neurobiology · 2024Article
- Death-associated protein kinase 1 as a therapeutic target for Alzheimer's disease.Translational neurodegeneration · 2024Review
- Alzheimer's Disease and Cancer: Common Targets.Mini reviews in medicinal chemistry · 2024Review
- Knockdown of DAPK1 inhibits IL-1β-induced inflammation and cartilage degradation in human chondrocytes by modulating the PEDF-mediated NF-κB and NLRP3 inflammasome pathway.Innate immunity · 2024Article
- Death-associated protein kinase 1 phosphorylates MDM2 and inhibits its protein stability and function.Archives of pharmacal research · 2023Article
- Mitochondrial Reactive Oxygen Species and Lytic Programmed Cell Death in Acute Inflammation.Antioxidants & redox signaling · 2023Review
- Autophagy and mitophagy-related extracellular mitochondrial dysfunction of cerebrospinal fluid cells in patients with hemorrhagic moyamoya disease.Scientific reports · 2023Article
7 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Necrosis and apoptosis are two distinct types of mechanisms that mediate ischemic injury. But a signaling point of convergence between them has yet to be identified. Here, we show that activated death-associated protein kinase 1 (DAPK1), phosphorylates p53 at serine-23 (pS(23)) via a direct binding of DAPK1 death domain (DAPK1DD) to the DNA binding motif of p53 (p53DM). We uncover that the pS(23) acts as a functional version of p53 and mediates necrotic and apoptotic neuronal death; in the nucleus, pS(23) induces the expression of proapoptotic genes, such as Bax, whereas in the mitochondrial matrix, pS(23) triggers necrosis via interaction with cyclophilin D (CypD) in cultured cortical neurons from mice. Deletion of DAPK1DD (DAPK1(DDΔ)) or application of Tat-p53DM that interrupts DAPK1-p53 interaction blocks these dual pathways of pS(23) actions in mouse cortical neurons. Thus, the DAPK1-p53 interaction is a signaling point of convergence of necrotic and apoptotic pathways and is a desirable target for the treatment of ischemic insults.
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