ArticleMolecular and cellular biology2008
Mdm2 promotes genetic instability and transformation independent of p53.
Article in Molecular and cellular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 2 of them syntheses that pooled it.
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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
69 citing papers in PubMed, 2 syntheses or guidelines pooled it, 105 citations in OpenAlex.
- MDM2 SNP309 is an ethnicity-dependent risk factor for digestive tract cancers.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Pooled it
- MDM2 SNP309, gene-gene interaction, and tumor susceptibility: an updated meta-analysis.BMC cancer · 2011Pooled it
- Helicobacter pylori Lipopolysaccharide Upregulates MDM2 via the TLR4/MAPK/AP-1 Pathway to Promote Gastric Cancer Progression.Digestive diseases and sciences · 2026Article
- Review
- Modulating the p53-MDM2 pathway: the therapeutic potential of natural compounds in cancer treatment.EXCLI journal · 2024Review
- Diagnostic value of MDM2 RNA in situ hybridization for low-grade osteosarcoma: Consistency comparison of RNA in situ hybridization, fluorescence in situ hybridization, and immunohistochemistry.Virchows Archiv : an international journal of pathology · 2023Article
- MDM2 Implications for Potential Molecular Pathogenic Therapies of Soft-Tissue Tumors.Journal of clinical medicine · 2023Review
- Targeted MDM2 Degradation Reveals a New Vulnerability for p53-Inactivated Triple-Negative Breast Cancer.Cancer discovery · 2023Article
- Resistance mechanisms to inhibitors of p53-MDM2 interactions in cancer therapy: can we overcome them?Cellular & molecular biology letters · 2021Review
- Article
- TRIM47 promotes malignant progression of renal cell carcinoma by degrading P53 through ubiquitination.Cancer cell international · 2021Article
- Mdm4 supports DNA replication in a p53-independent fashion.Oncogene · 2020Article
- Structural basis for DNA damage-induced phosphoregulation of MDM2 RING domain.Nature communications · 2020Article
- Drug Development Targeting the Ubiquitin-Proteasome System (UPS) for the Treatment of Human Cancers.Cancers · 2020Review
- Targeting Mouse Double Minute 2: Current Concepts in DNA Damage Repair and Therapeutic Approaches in Cancer.Frontiers in pharmacology · 2020Review
- Smarcal1 and Zranb3 Protect Replication Forks from Myc-Induced DNA Replication Stress.Cancer research · 2019Article
- The 40bp indel polymorphism ofMolecular biology research communications · 2019Article
- Functional role of RRS1 in breast cancer cell proliferation.Journal of cellular and molecular medicine · 2018Article
- Chromatin modifiers Mdm2 and RNF2 prevent RNA:DNA hybrids that impair DNA replication.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Lifestyle chemical carcinogens associated with mutations in cell cycle regulatory genes increases the susceptibility to gastric cancer risk.Environmental science and pollution research international · 2018Article
9 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
4 authors at 2 institutions in 1 country.
Funding
Abstract
Mdm2, a regulator of the tumor suppressor p53, is frequently overexpressed in human malignancies. Mdm2 also has unresolved, p53-independent functions that contribute to tumorigenesis. Here, we show that increased Mdm2 expression induced chromosome/chromatid breaks and delayed DNA double-strand break repair in cells lacking p53 but not in cells with a mutant form of Nbs1, a component of the Mre11/Rad50/Nbs1 DNA repair complex. A 31-amino-acid region of Mdm2 was necessary for binding to Nbs1. Mutation of conserved amino acids in the Nbs1 binding domain of Mdm2 inhibited Mdm2-Nbs1 association and prevented Mdm2 from delaying phosphorylation of H2AX and ATM-S/TQ sites, repair of DNA breaks, and resolution of DNA damage foci. Similarly, the mutation of eight amino acids in the Mdm2 binding domain of Nbs1 inhibited Mdm2-Nbs1 interaction and blocked the ability of Mdm2 to delay DNA break repair. Both Nbs1 and ATM, but not the ubiquitin ligase activity of Mdm2, were necessary to inhibit DNA break repair. Only Mdm2 with an intact Nbs1 binding domain was able to increase the frequency of chromosome/chromatid breaks and the transformation efficiency of cells lacking p53. Therefore, the interaction of Mdm2 with Nbs1 inhibited DNA break repair, leading to chromosome instability and subsequent transformation that was independent of p53.
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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.