ArticleCancer research2008
MDM2 regulates dihydrofolate reductase activity through monoubiquitination.
Article in Cancer research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 50 citations in OpenAlex.
- Review
- Urinary metabolite model to predict the dying process in lung cancer patients.Communications medicine · 2025Article
- Dual inhibitor of MDM2 and NFAT1 for experimental therapy of breast cancer:Frontiers in pharmacology · 2025Article
- Cycling back to folate metabolism in cancer.Nature cancer · 2024Review
- Modulating the p53-MDM2 pathway: the therapeutic potential of natural compounds in cancer treatment.EXCLI journal · 2024Review
- Regulatory mechanisms of one-carbon metabolism enzymes.The Journal of biological chemistry · 2023Review
- MDM2 Implications for Potential Molecular Pathogenic Therapies of Soft-Tissue Tumors.Journal of clinical medicine · 2023Review
- Drug repositioning for esophageal squamous cell carcinoma.Frontiers in genetics · 2022Article
- Review
- TP53 mutations in head and neck cancer cells determine the Warburg phenotypic switch creating metabolic vulnerabilities and therapeutic opportunities for stratified therapies.Cancer letters · 2020Article
- Review
- Targeting MDM2 for novel molecular therapy: Beyond oncology.Medicinal research reviews · 2020Review
- Inhibition of DYRK1A-EGFR axis by p53-MDM2 cascade mediates the induction of cellular senescence.Cell death & disease · 2019Article
- Loss of Diacylglycerol Kinase-Ζ Inhibits Cell Proliferation and Survival in Human Gliomas.Molecular neurobiology · 2016Article
- Mouse double minute 2 (MDM2) upregulates Snail expression and induces epithelial-to-mesenchymal transition in breast cancer cells in vitro and in vivo.Oncotarget · 2016Article
- Article
- A Novel Interaction between TFII-I and Mdm2 with a Negative Effect on TFII-I Transcriptional Activity.PloS one · 2015Article
- MDM2 mediates nonproteolytic polyubiquitylation of the DEAD-Box RNA helicase DDX24.Molecular and cellular biology · 2014Article
- MDM2's social network.Oncogene · 2014Review
- Targeting MDM2-p53 interaction for cancer therapy: are we there yet?Current medicinal chemistry · 2014Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
MDM2 is a ubiquitin ligase that is best known for its essential function in the negative regulation of p53. In addition, MDM2 expression is associated with tumor progression in a number of common cancers, and in some cases, this has been shown to be independent of p53 status. MDM2 has been shown to promote the degradation of a number of other proteins involved in the regulation of normal cell growth and proliferation, including MDM4 and RB1. Here, we describe the identification of a novel substrate for the MDM2 ubiquitin ligase: dihydrofolate reductase (DHFR). MDM2 binds directly to DHFR and catalyses its monoubiquitination and not its polyubiquitination. In addition, MDM2 expression reduces DHFR activity in a p53-independent manner, but has no effect upon the steady-state level of expression of DHFR. We show that changes in MDM2 expression alter folate metabolism in cells as evidenced by MDM2-dependent alteration in the sensitivity of cells to the antifolate drug methotrexate. Furthermore, we show that the ability of MDM2 to inhibit DHFR activity depends upon an intact MDM2 RING finger. Our studies provide for the first time a link between MDM2, an oncogene with a critical ubiquitin ligase activity and a vital one-carbon donor pathway involved in epigenetic regulation, and DNA metabolism, which has wide ranging implications for both cell biology and tumor development.
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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.