ArticleNature cell biology2023
De novo pyrimidine biosynthetic complexes support cancer cell proliferation and ferroptosis defence.
Article in Nature cell biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
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Who cites it
94 citing papers in PubMed, 101 citations in OpenAlex.
- OTUD6A promotes de novo pyrimidine synthesis by deubiquitinating and stabilizing CAD in cervical cancer.Oncogene · 2026Article
- DH-AUTAC induces ferroptosis in colorectal cancer by targeting DHODH for autophagic degradation through KCTD10-SQSTM1 signaling.Journal of gastroenterology · 2026Article
- Dynamic control of nucleotide metabolism in physiology and disease.Nature cell biology · 2026Review
- Arginine metabolism supportsmBio · 2026Article
- DHODH-Mediated Suppression of Ferroptosis Supports Radioresistance and Represents a Therapeutic Vulnerability in Lung Cancer.Cancer research · 2026Article
- Centella Asiatica Alleviates Type 2 Diabetes-Related Hepatic Glycolipid Disorders via Regulating UPP1-Mediated Pyrimidine Metabolism.Current issues in molecular biology · 2026Article
- Effects of Sodium Butyrate on Digestive Metabolism, Blood Gas Parameters and Blood Biochemical Indices in Tumbler Pigeons Based on Untargeted Metabolomics.Animals : an open access journal from MDPI · 2026Article
- Oncolytic virus hijacks GOT1 and pyrimidinosomes to fuel pyrimidine synthesis for replication in tumor cells.Tumour virus research · 2026Article
- Translating ferroptosis into oncology: challenges, opportunities and future directions.Nature reviews. Clinical oncology · 2026Review
- Extracellular Vesicle-Transferred ATP-Citrate Lyase Induces Monocyte Differentiation Toward Tumor-Associated Macrophages and Fuels Hepatocellular Carcinoma Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Myricetin InhibitsCells · 2026Article
- Metronomic Capecitabine Triggers Ferroptosis in Hepatocellular Carcinoma Cells Through Inhibition of TYMS.Cancer medicine · 2026Article
- Integrating single-cell RNA and bulk RNA sequencing data to identify prognostic genes associated with pyrimidine metabolism in triple-negative breast cancer by machine learning algorithm combinations.Discover oncology · 2026Article
- TGM2-mediated serotonylation of GPX4 confers ferroptosis resistance to promote gastric tumorigenesis.Cell discovery · 2026Article
- Ferroptosis in Neuropsychiatric and Neurodegenerative Disorders: Shared Mechanisms and Disease-Specific Signatures.Pharmaceuticals (Basel, Switzerland) · 2026Review
- The oncogenic control of nucleotide synthesis.Oncogenesis · 2026Review
- Targeting ferroptosis in cancer: from mechanistic insights to therapeutic approaches.Molecular biomedicine · 2026Review
- Mitochondrial Transfer Rescues Respiration to Support De Novo Pyrimidine Biosynthesis and Tumor Progression.Cancer research · 2026Article
- Antibody‒drug conjugates with DHODH inhibitor as novel payload class for cancer and SARS-CoV-2 infection therapies.Acta pharmaceutica Sinica. B · 2026Article
- Research progress on the regulation of ferroptosis in NPC (Review).Oncology reports · 2026Review
34 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
De novo pyrimidine biosynthesis is achieved by cytosolic carbamoyl-phosphate synthetase II, aspartate transcarbamylase and dihydroorotase (CAD) and uridine 5'-monophosphate synthase (UMPS), and mitochondrial dihydroorotate dehydrogenase (DHODH). However, how these enzymes are orchestrated remains enigmatical. Here we show that cytosolic glutamate oxaloacetate transaminase 1 clusters with CAD and UMPS, and this complex then connects with DHODH, which is mediated by the mitochondrial outer membrane protein voltage-dependent anion-selective channel protein 3. Therefore, these proteins form a multi-enzyme complex, named 'pyrimidinosome', involving AMP-activated protein kinase (AMPK) as a regulator. Activated AMPK dissociates from the complex to enhance pyrimidinosome assembly but inactivated UMPS, which promotes DHODH-mediated ferroptosis defence. Meanwhile, cancer cells with lower expression of AMPK are more reliant on pyrimidinosome-mediated UMP biosynthesis and more vulnerable to its inhibition. Our findings reveal the role of pyrimidinosome in regulating pyrimidine flux and ferroptosis, and suggest a pharmaceutical strategy of targeting pyrimidinosome in cancer treatment.
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