ArticlemBio2017
A Critical Role of Glutamine and Asparagine γ-Nitrogen in Nucleotide Biosynthesis in Cancer Cells Hijacked by an Oncogenic Virus.
Article in mBio, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 89 citations in OpenAlex.
- Glutamine metabolism in health and disease.Signal transduction and targeted therapy · 2026Review
- Metabolomic Analysis of Lytic KSHV Infection: Induced Host Nucleotide Metabolism Is Required for Infectious Virus Production.Viruses · 2026Article
- Microbiota in cancer: current understandings and future perspectives.Signal transduction and targeted therapy · 2026Review
- Outsourcing of energetically costly amino acids at the origin of animals.Nature communications · 2026Article
- Hypoxic microenvironment in cancer: role in metabolic reprogramming.Frontiers in oncology · 2026Review
- WSSV-induced reversal of the malate-aspartate shuttle facilitates viral replication in shrimp hemocytes.Cell communication and signaling : CCS · 2025Article
- African swine fever virus hijacks host pyrimidine metabolism to promote viral replication.Journal of virology · 2025Article
- A viral Cyclin D homolog protein hijacks the metabolic stress sensor SESN2 to promote primary effusion lymphoma growth.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Oncogenic Mechanisms of Kaposi's Sarcoma-Associated Herpesvirus on Cell Metabolism and Cell Transformation.Journal of medical virology · 2025Review
- Viral Reprogramming of Nucleotide Synthesis and Its Impact on Viral Infection.Journal of medical virology · 2025Review
- Review
- Metabolic Imprint of Poliovirus on Glioblastoma Cells and Its Role in Virus Replication and Cytopathic Activity.International journal of molecular sciences · 2025Article
- Impacts of 360 mg/kg Niacinamide Supplementation in Low-Protein Diets on Energy and Nitrogen Metabolism and Intestinal Microbiota in Growing-Finishing Pigs.Animals : an open access journal from MDPI · 2025Article
- Article
- Sex-specific effects of exogenous asparagine on colorectal tumor growth, 17β-estradiol levels, and aromatase.Pharmacological research · 2025Article
- Analysis of Metabolomic Reprogramming Induced by Infection with Kaposi's Sarcoma-Associated Herpesvirus Using Untargeted Metabolomic Profiling.International journal of molecular sciences · 2025Article
- Dietary supplementation with glutamate improves the flesh quality of gibel carp (Journal of nutritional science · 2025Article
- Microbial metabolites in tumor metabolic reprogramming and immunotherapy: new insights.Frontiers in cellular and infection microbiology · 2025Review
- Understanding Metabolic Pathway Rewiring by Oncogenic Gamma Herpesvirus.Journal of microbiology and biotechnology · 2024Review
- Metabolism of asparagine in the physiological state and cancer.Cell communication and signaling : CCS · 2024Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
While glutamine is a nonessential amino acid that can be synthesized from glucose, some cancer cells primarily depend on glutamine for their growth, proliferation, and survival. Numerous types of cancer also depend on asparagine for cell proliferation. The underlying mechanisms of the glutamine and asparagine requirement in cancer cells in different contexts remain unclear. In this study, we show that the oncogenic virus Kaposi's sarcoma-associated herpesvirus (KSHV) accelerates the glutamine metabolism of glucose-independent proliferation of cancer cells by upregulating the expression of numerous critical enzymes, including glutaminase 2 (GLS2), glutamate dehydrogenase 1 (GLUD1), and glutamic-oxaloacetic transaminase 2 (GOT2), to support cell proliferation. Surprisingly, cell crisis is rescued only completely by supplementation with asparagine but minimally by supplementation with α-ketoglutarate, aspartate, or glutamate upon glutamine deprivation, implying an essential role of γ-nitrogen in glutamine and asparagine for cell proliferation. Specifically, glutamine and asparagine provide the critical γ-nitrogen for purine and pyrimidine biosynthesis, as knockdown of four rate-limiting enzymes in the pathways, including carbamoylphosphate synthetase 2 (CAD), phosphoribosyl pyrophosphate amidotransferase (PPAT), and phosphoribosyl pyrophosphate synthetases 1 and 2 (PRPS1 and PRPS2, respectively), suppresses cell proliferation. These findings indicate that glutamine and asparagine are shunted to the biosynthesis of nucleotides and nonessential amino acids from the tricarboxylic acid (TCA) cycle to support the anabolic proliferation of KSHV-transformed cells. Our results illustrate a novel mechanism by which an oncogenic virus hijacks a metabolic pathway for cell proliferation and imply potential therapeutic applications in specific types of cancer that depend on this pathway.
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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.