ArticleThe Journal of biological chemistry2018
Purine nucleotide metabolism regulates expression of the human immune ligand MICA.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- Circulating natural killer cells are phenotypically and functionally altered in age-related macular degeneration.Cell reports. Medicine · 2026Article
- Rewiring cancer metabolism: oncogenic signaling pathways and targeted therapeutics.Science China. Life sciences · 2025Review
- Dichloroacetate enhances Chemo-sensitivity in wild-type P53 breast cancer cells by modulating ABCG2 and NKG2DL.Scientific reports · 2025Article
- Skin Metabolic Signatures of Psoriasis and Psoriasis Concurrent with Metabolic Syndrome.Journal of inflammation research · 2025Article
- Immunosurveillance encounters cancer metabolism.EMBO reports · 2024Review
- The metabolism of cells regulates their sensitivity to NK cells depending on p53 status.Scientific reports · 2022Article
- Mitochondrial Function and Microbial Metabolites as Central Regulators of Intestinal Immune Responses and Cancer.Frontiers in microbiology · 2022Article
- Effects of metabolic cancer therapy on tumor microenvironment.Frontiers in oncology · 2022Review
- A four immune-related long noncoding RNAs signature as predictors for cervical cancer.Human cell · 2022Article
- Interplay of Immunometabolism and Epithelial-Mesenchymal Transition in the Tumor Microenvironment.International journal of molecular sciences · 2021Review
- Review
- Exometabolomic Analysis of Decidualizing Human Endometrial Stromal and Perivascular Cells.Frontiers in cell and developmental biology · 2021Article
- Inosine pranobex enhances human NK cell cytotoxicity by inducing metabolic activation and NKG2D ligand expression.European journal of immunology · 2020Article
- Cytoplasmic Citrate Flux Modulates the Immune Stimulatory NKG2D Ligand MICA in Cancer Cells.Frontiers in immunology · 2020Article
- Hyperglycemia Associated Metabolic and Molecular Alterations in Cancer Risk, Progression, Treatment, and Mortality.Cancers · 2019Review
- Intragenic transcriptional interference regulates the human immune ligand MICA.The EMBO journal · 2018Article
- Tumor Microenvironment-Induced Immunometabolic Reprogramming of Natural Killer Cells.Frontiers in immunology · 2018Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Expression of the cell-surface glycoprotein MHC class I polypeptide-related sequence A (MICA) is induced in dangerous, abnormal, or "stressed" cells, including cancer cells, virus-infected cells, and rapidly proliferating cells. MICA is recognized by the activating immune cell receptor natural killer group 2D (NKG2D), providing a mechanism by which immune cells can identify and potentially eliminate pathological cells. Immune recognition through NKG2D is implicated in cancer, atherosclerosis, transplant rejection, and inflammatory diseases, such as rheumatoid arthritis. Despite the wide range of potential therapeutic applications of MICA manipulation, the factors that control MICA expression are unclear. Here we use metabolic interventions and metabolomic analyses to show that the transition from quiescent cellular metabolism to a "Warburg" or biosynthetic metabolic state induces MICA expression. Specifically, we show that glucose transport into the cell and active glycolytic metabolism are necessary to up-regulate MICA expression. Active purine synthesis is necessary to support this effect of glucose, and increases in purine nucleotide levels are sufficient to induce MICA expression. Metabolic induction of MICA expression directly influences NKG2D-dependent cytotoxicity by immune cells. These findings support a model of MICA regulation whereby the purine metabolic activity of individual cells is reflected by cell-surface MICA expression and is the subject of surveillance by NKG2D receptor-expressing immune cells.
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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.