ArticleGenes & development2001
ATM-dependent phosphorylation of Mdm2 on serine 395: role in p53 activation by DNA damage.
Article in Genes & development, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 275 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
275 citing papers in PubMed, 1 synthesis or guideline pooled it, 702 citations in OpenAlex.
- MDM2 SNP309 polymorphism is associated with colorectal cancer risk.Scientific reports · 2014Pooled it
- Advances in ferroptosis for castration-resistant prostate cancer treatment: novel drug targets and combination therapy strategies.Prostate cancer and prostatic diseases · 2026Review
- NOTCH1 intracellular domain stabilization by MDM2 plays a major role in NSCLC response to platinum.EMBO molecular medicine · 2026Article
- Targeting ATR-CHK1 and ATM-CHK2 Axes in Pancreatic Cancer-A Comprehensive Review of Literature.International journal of molecular sciences · 2026Review
- E3 ubiquitin ligases orchestrate chemo-resistance in gastrointestinal malignancies: from DNA damage response to therapeutic targeting.Frontiers in oncology · 2026Review
- XPC Deficiency Activate Cisplatin-Mediated Autophagy in Bladder Cancer by Limiting Novel PHRF1-Mediated Ubiquitination of the p53 Protein.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cell confluency affects p53 dynamics in response to DNA damage.Molecular biology of the cell · 2025Article
- Deciphering UBE4B phosphorylation dynamics: a key mechanism in p53 accumulation and cancer cell response to DNA damage.Cell death discovery · 2025Article
- Canonical and noncanonical NOTCH signaling in the nongenetic resistance of cancer: distinct and concerted control.Frontiers of medicine · 2025Review
- Coronin 2B deficiency induces nucleolar stress and neuronal apoptosis.Cell death & disease · 2024Article
- Metabolic Roles of HIF1, c-Myc, and p53 in Glioma Cells.Metabolites · 2024Review
- Spotlight on G-Quadruplexes: From Structure and Modulation to Physiological and Pathological Roles.International journal of molecular sciences · 2024Review
- Modulating the p53-MDM2 pathway: the therapeutic potential of natural compounds in cancer treatment.EXCLI journal · 2024Review
- Making gene editing accessible in resource limited environments: recommendations to guide a first-time user.Frontiers in genome editing · 2024Review
- Permission to pass: on the role of p53 as a gatekeeper for aneuploidy.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2023Review
- Multiple sevoflurane exposures during mid-trimester induce neurotoxicity in the developing brain initiated by 15LO2-Mediated ferroptosis.CNS neuroscience & therapeutics · 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
- Article
- Use ofHeliyon · 2023Article
- Review
215 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
The p53 tumor suppressor protein, a key regulator of cellular responses to genotoxic stress, is stabilized and activated after DNA damage. The rapid activation of p53 by ionizing radiation and radiomimetic agents is largely dependent on the ATM kinase. p53 is phosphorylated by ATM shortly after DNA damage, resulting in enhanced stability and activity of p53. The Mdm2 oncoprotein is a pivotal negative regulator of p53. In response to ionizing radiation and radiomimetic drugs, Mdm2 undergoes rapid ATM-dependent phosphorylation prior to p53 accumulation. This results in a decrease in its reactivity with the 2A10 monoclonal antibody. Phage display analysis identified a consensus 2A10 recognition sequence, possessing the core motif DYS. Unexpectedly, this motif appears twice within the human Mdm2 molecule, at positions corresponding to residues 258-260 and 393-395. Both putative 2A10 epitopes are highly conserved and encompass potential phosphorylation sites. Serine 395, residing within the carboxy-terminal 2A10 epitope, is the major target on Mdm2 for phosphorylation by ATM in vitro. Mutational analysis supports the conclusion that Mdm2 undergoes ATM-dependent phosphorylation on serine 395 in vivo in response to DNA damage. The data further suggests that phosphorylated Mdm2 may be less capable of promoting the nucleo-cytoplasmic shuttling of p53 and its subsequent degradation, thereby enabling p53 accumulation. Our findings imply that activation of p53 by DNA damage is achieved, in part, through attenuation of the p53-inhibitory potential of Mdm2.
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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.