ArticleNature cell biology2009
Phosphorylation of ATM by Cdk5 mediates DNA damage signalling and regulates neuronal death.
Article in Nature cell biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 98 papers.
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.
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
98 citing papers in PubMed, 179 citations in OpenAlex.
- Cyclins and Cyclin-Dependent Kinases: Structure, Biological Functions, and Innovative Targeting Strategies in Cancer.MedComm · 2026Review
- Proteomic Characterization of Replication Stress and Impaired Antioxidant Defense in Tacrolimus-Induced Chronic Nephrotoxicity.International journal of molecular sciences · 2026Article
- Comparative Proteomic Analysis of Self-CompatiblePlant direct · 2025Article
- The Duality of Cdk5: A Master Regulator in Neurodevelopment and a Hijacked Oncogene in Cancer.Cells · 2025Review
- Integrated genomics reveals cellular senescence-driven molecular networks and immune crosstalk in myopia pathogenesis.Journal of cell communication and signaling · 2025Article
- Protein kinases in neurodegenerative diseases: current understandings and implications for drug discovery.Signal transduction and targeted therapy · 2025Review
- CDK5: Insights into its roles in diseases.Molecular biology reports · 2025Review
- Protein Kinase C-Delta Mediates Cell Cycle Reentry and Apoptosis Induced by Amyloid-Beta Peptide in Post-Mitotic Cortical Neurons.International journal of molecular sciences · 2024Article
- Intergenerational epigenetic inheritance mediated by MYS-2/MOF in the pathogenesis of Alzheimer's disease.iScience · 2024Article
- Unveiling Potential Neurotoxic Mechansisms: Pb-Induced Activation of CDK5-p25 Signaling Axis in Alzheimer's Disease Development, Emphasizing CDK5 Inhibition and Formation of Toxic p25 Species.Molecular neurobiology · 2024Article
- Dinaciclib synergizes with BH3 mimetics targeting BCL-2 and BCL-XMolecular oncology · 2023Article
- TP5: A Novel Therapeutic Approach Targeting Aberrant and Hyperactive CDK5/p25 for the Treatment of Colorectal Carcinoma.International journal of molecular sciences · 2023Article
- Maintaining Genome Integrity: Protein Kinases and Phosphatases Orchestrate the Balancing Act of DNA Double-Strand Breaks Repair in Cancer.International journal of molecular sciences · 2023Review
- Sting and p53 DNA repair pathways are compromised in Alzheimer's disease.Scientific reports · 2023Article
- Multimodal perturbation analyses of cyclin-dependent kinases reveal a network of synthetic lethalities associated with cell-cycle regulation and transcriptional regulation.Scientific reports · 2023Article
- A Cdk5-derived peptide inhibits Cdk5/p25 activity and improves neurodegenerative phenotypes.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Protein post-translational modifications in the regulation of cancer hallmarks.Cancer gene therapy · 2023Review
- Phospho-heavy-labeled-spiketide FAIMS stepped-CV DDA (pHASED) provides real-time phosphoproteomics data to aid in cancer drug selection.Clinical proteomics · 2022Article
- Phosphorylation of BRCA1 by ATM upon double-strand breaks impacts ATM function in end-resection: A potential feedback loop.iScience · 2022Article
- Article
38 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The phosphatidylinositol-3-kinase-like kinase ATM (ataxia-telangiectasia mutated) has a central role in coordinating DNA damage responses, including cell-cycle checkpoint control, DNA repair and apoptosis. Mutations of ATM cause a spectrum of defects ranging from neurodegeneration to cancer predisposition. However, the mechanism by which DNA damage activates ATM is poorly understood. Here we show that Cdk5 (cyclin-dependent kinase 5), activated by DNA damage, directly phosphorylates ATM at Ser 794 in post-mitotic neurons. Phosphorylation at Ser 794 precedes, and is required for, ATM autophosphorylation at Ser 1981, and activates ATM kinase activity. The Cdk5-ATM signal regulates phosphorylation and function of the ATM targets p53 and H2AX. Interruption of the Cdk5-ATM pathway attenuates DNA-damage-induced neuronal cell cycle re-entry and expression of the p53 targets PUMA and Bax, protecting neurons from death. Thus, activation of Cdk5 by DNA damage serves as a critical signal to initiate the ATM response and regulate ATM-dependent cellular processes.
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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.