ArticleMolecular cancer2024
The DNA damage sensor ATM kinase interacts with the p53 mRNA and guides the DNA damage response pathway.
Article in Molecular cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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
25 citing papers in PubMed, 37 citations in OpenAlex.
- A Toxoplasma gondii-derived ROP38 protein engages Ser15/Thr18-linked p53 activation and DNA damage-associated apoptotic signaling in human cancer cells.Cell communication and signaling : CCS · 2026Article
- Potential Mechanisms of MAP Kinase JNK's Involvement in Modulating Cancer Cell Fate in a Cisplatin Concentration-Dependent Manner.Pharmaceuticals (Basel, Switzerland) · 2026Article
- HRD in endometrial cancer: LST loss drives distinct genomic profile and platinum response.NPJ precision oncology · 2026Article
- A Review of Ionizing Radiation-Induced Senescence of Bone Marrow Mesenchymal Stem/Stromal Cells: Mechanisms and Therapeutic Strategies.Current issues in molecular biology · 2026Review
- From concept to application: Exploring the evolution and potential of DUBTAC technology.Acta pharmaceutica Sinica. B · 2026Review
- Stratified and Quantified Score Construction of Low-Grade Glioma Samples Based on TP53 Signaling Pathway.BioMed research international · 2026Article
- Glutamine metabolism and its roles in tumor radiotherapy by regulating DNA damage repair.Frontiers in cell and developmental biology · 2026Review
- Integrative multi-omics profiling identifies infiltrative hepatocellular carcinoma as an immunotherapy-resistant subtype with distinct molecular features.Clinical and molecular hepatology · 2026Article
- Reduced structural rigidity of MDMX protein enhances binding to TP53 mRNA.Bioscience reports · 2025Article
- TheiScience · 2025Article
- ATM deficiency drives phenotypic diversity and Purkinje cell degeneration in a macaque model of ataxia-telangiectasia.Cell reports. Medicine · 2025Article
- Epigenetic Regulation of Aging and its Rejuvenation.MedComm · 2025Review
- DNA damage response and cell fate decisions across the lifespan: from fetal development to age-related respiratory diseases.Cell & bioscience · 2025Review
- ATM and p53 in aging and cancer: a double-edged sword in genomic integrity.Biogerontology · 2025Review
- Germline-Somatic Interactions in BRCA-Associated Cancers: Unique Molecular Profiles and Clinical Outcomes Linking ATM to TP53 Synthetic Essentiality.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Targeting NSCLC drug resistance: Systems biology insights into the MALAT1/miR-145-5p axis and Wip1 in regulating ferroptosis and apoptosis.Journal of the Royal Society, Interface · 2025Article
- IHCH9033, a novel class I HDAC inhibitor, synergizes with FLT3 inhibitor and rescues quizartinib resistance in FLT3-ITD AML via enhancing DNA damage response.Experimental hematology & oncology · 2025Article
- Manganese mediates antiviral effects by driving an ATM -TBK1 phosphorylation signaling pathway.Frontiers in immunology · 2025Article
- Melatonin ameliorates zearalenone-induced ovarian damage in mice through antioxidative effects.Frontiers in veterinary science · 2025Article
- Computer-aided Drug Discovery of Epigenetic Modulators in Dual-target Therapy of Multifactorial Diseases.Current topics in medicinal chemistry · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 5 institutions in 4 countries.
Funding
Abstract
backgroundThe ATM kinase constitutes a master regulatory hub of DNA damage and activates the p53 response pathway by phosphorylating the MDM2 protein, which develops an affinity for the p53 mRNA secondary structure. Disruption of this interaction prevents the activation of the nascent p53. The link of the MDM2 protein-p53 mRNA interaction with the upstream DNA damage sensor ATM kinase and the role of the p53 mRNA in the DNA damage sensing mechanism, are still highly anticipated.
methodsThe proximity ligation assay (PLA) has been extensively used to reveal the sub-cellular localisation of the protein-mRNA and protein-protein interactions. ELISA and co-immunoprecipitation confirmed the interactions in vitro and in cells.
resultsThis study provides a novel mechanism whereby the p53 mRNA interacts with the ATM kinase enzyme and shows that the L22L synonymous mutant, known to alter the secondary structure of the p53 mRNA, prevents the interaction. The relevant mechanistic roles in the DNA Damage Sensing pathway, which is linked to downstream DNA damage response, are explored. Following DNA damage (double-stranded DNA breaks activating ATM), activated MDMX protein competes the ATM-p53 mRNA interaction and prevents the association of the p53 mRNA with NBS1 (MRN complex). These data also reveal the binding domains and the phosphorylation events on ATM that regulate the interaction and the trafficking of the complex to the cytoplasm.
conclusionThe presented model shows a novel interaction of ATM with the p53 mRNA and describes the link between DNA Damage Sensing with the downstream p53 activation pathways; supporting the rising functional implications of synonymous mutations altering secondary mRNA structures.
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.