ArticleThe EMBO journal2002
Tyrosine phosphorylation of Mdm2 by c-Abl: implications for p53 regulation.
Article in The EMBO journal, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 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.
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Who cites it
78 citing papers in PubMed, 196 citations in OpenAlex.
- Integrative multi-omics analysis reveals lipid/metabolite dysregulation and temporal decoupling in disease progression.Scientific reports · 2026Article
- Article
- The Abl1 tyrosine kinase is a key player in doxorubicin-induced cardiomyopathy and its p53/p73 cell death mediated signaling differs in atrial and ventricular cardiomyocytes.Journal of translational medicine · 2024Article
- 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
- Association of p53 with Neurodegeneration in Parkinson's Disease.Parkinson's disease · 2022Review
- Parkin interacting substrate phosphorylation by c-Abl drives dopaminergic neurodegeneration.Brain : a journal of neurology · 2021Article
- ER stress-induced modulation of neural activity and seizure susceptibility is impaired in a fragile X syndrome mouse model.Neurobiology of disease · 2021Article
- Review
- Review
- Structural basis for DNA damage-induced phosphoregulation of MDM2 RING domain.Nature communications · 2020Article
- α-Synucleinopathy associated c-Abl activation causes p53-dependent autophagy impairment.Molecular neurodegeneration · 2020Article
- Targeting Mouse Double Minute 2: Current Concepts in DNA Damage Repair and Therapeutic Approaches in Cancer.Frontiers in pharmacology · 2020Review
- Entire ABL1 Gene Deletion Without BCR/ABL1 Rearrangement in a Female Patient with B-Cell Precursor Acute Lymphoblastic Leukemia.OncoTargets and therapy · 2020Article
- Interaction of Abl Tyrosine Kinases with SOCS3 Impairs Its Suppressor Function in Tumorigenesis.Neoplasia (New York, N.Y.) · 2018Article
- The Role of MDM2 in Promoting Genome Stability versus Instability.International journal of molecular sciences · 2017Review
- Mdm2 mediates FMRP- and Gp1 mGluR-dependent protein translation and neural network activity.Human molecular genetics · 2017Article
- Phosphorylation of the Mdm2 oncoprotein by the c-Abl tyrosine kinase regulates p53 tumor suppression and the radiosensitivity of mice.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- MDM2 oligomers: antagonizers of the guardian of the genome.Oncogene · 2016Review
- Intra molecular interactions in the regulation of p53 pathway.Translational cancer research · 2016Article
- Regulation of the Mdm2-p53 signaling axis in the DNA damage response and tumorigenesis.Translational cancer research · 2016Article
18 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
9 authors.
Funding
Abstract
The p53 tumor suppressor is inhibited and destabilized by Mdm2. However, under stress conditions, this downregulation is relieved, allowing the accumulation of biologically active p53. Recently we showed that c-Abl is important for p53 activation under stress conditions. In response to DNA damage, c-Abl protects p53 by neutralizing the inhibitory effects of Mdm2. In this study we ask whether this neutralization involves a direct interplay between c-Abl and Mdm2, and what is the contribution of the c-Abl kinase activity? We demonstrate that the kinase activity of c-Abl is required for maintaining the basal levels of p53 expression and for achieving maximal accumulation of p53 in response to DNA damage. Importantly, c-Abl binds and phosphorylates Mdm2 in vivo and in vitro. We characterize Hdm2 (human Mdm2) phosphorylation at Tyr394. Substitution of Tyr394 by Phe394 enhances the ability of Mdm2 to promote p53 degradation and to inhibit its transcriptional and apoptotic activities. Our results suggest that phosphorylation of Mdm2 by c-Abl impairs the inhibition of p53 by Mdm2, hence defining a novel mechanism by which c-Abl activates p53.
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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.