ArticleProceedings of the National Academy of Sciences of the United States of America2021
p53 deficiency induces MTHFD2 transcription to promote cell proliferation and restrain DNA damage.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 74 citations in OpenAlex.
- The mitochondrial chaperone HSPD1 folds MTHFD2 independently of its co-chaperone HSPE1.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Article
- The p53-Associated Regulation of ATF4 mRNA Expression Involves p21 and p130 in a Stress-Dependent Manner.Cells · 2026Article
- miR-1251-5p inhibits tumorigenesis and metastasis in renal cell carcinoma by targeting MTHFD2.Translational andrology and urology · 2026Article
- Review
- MTHFD2: a promising metabolic checkpoint for diseases.Journal of translational medicine · 2026Review
- Hallmarks of nuclear metabolism: implications for genome integrity, nuclear signaling, and therapeutic targeting.npj metabolic health and disease · 2026Review
- MTHFD2 is required for DNA repair and implicated in LUAD radiotherapy resistance.Journal of translational medicine · 2026Article
- SOX4-STAT6-MTHFD2 axis drives hepatocellular carcinoma progression and treatment resistance.Cell death & disease · 2026Article
- The impact of p53 mutation on tumor immune evasion: mechanistic insights and clinical implications.Frontiers in immunology · 2026Review
- Photothermal therapy triggering organelle stress and metabolic reprogramming to potentiate antitumor immunity.Frontiers in immunology · 2026Review
- One-carbon metabolism in cancer: moonlighting functions of metabolic enzymes and anti-tumor therapy.Cancer metastasis reviews · 2025Review
- MTHFD2: A Retrospective and a Glance into the Future.International journal of molecular sciences · 2025Review
- Mono-ADP-ribosylating PARP enzymes in cellular signaling and disease.Journal of cell science · 2025Review
- MTHFD2 marks pemetrexed resistance in pulmonary adenocarcinoma with EGFR wild type.Discover oncology · 2025Article
- Metabolic regulation by p53: Implications for cancer therapy.Molecules and cells · 2025Review
- Therapeutic targeting de novo purine biosynthesis driven by β-catenin-dependent PPAT upregulation in hepatoblastoma.Cell death & disease · 2025Article
- Metabolic determinants of germinal center B cell formation and responses.Nature chemical biology · 2025Article
- Metabolic Rewiring in the Face of Genomic Assault: Integrating DNA Damage Response and Cellular Metabolism.Biomolecules · 2025Review
- Harnessing multi-omics and artificial intelligence: revolutionizing prognosis and treatment in hepatocellular carcinoma.Frontiers in immunology · 2025Article
- Anticancer effects and mechanisms ofComputational and structural biotechnology journal · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer cells acquire metabolic reprogramming to satisfy their high biogenetic demands, but little is known about how metabolic remodeling enables cancer cells to survive stress associated with genomic instability. Here, we show that the mitochondrial methylenetetrahydrofolate dehydrogenase (MTHFD2) is transcriptionally suppressed by p53, and its up-regulation by p53 inactivation leads to increased folate metabolism, de novo purine synthesis, and tumor growth in vivo and in vitro. Moreover, MTHFD2 unexpectedly promotes nonhomologous end joining in response to DNA damage by forming a complex with PARP3 to enhance its ribosylation, and the introduction of a PARP3-binding but enzymatically inactive MTHFD2 mutant (e.g., D155A) sufficiently prevents DNA damage. Notably, MTHFD2 depletion strongly restrains p53-deficient cell proliferation and sensitizes cells to chemotherapeutic agents, indicating a potential role for MTHFD2 depletion in the treatment of p53-deficient tumors.
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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.