ArticleThe Journal of biological chemistry2020
Development of cGAMP-Luc, a sensitive and precise coupled enzyme assay to measure cGAMP in complex biological samples.
Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- A direct, real-time, spectrophotometric assay for measuring ENPP1-catalyzed cGAMP hydrolysis.The Journal of biological chemistry · 2026Article
- ENPP1 inhibitor with ultralong drug-target residence time as an innate immune checkpoint blockade cancer therapy.Cell reports. Medicine · 2025Article
- Structural insight into the cGAS active site explains differences between therapeutically relevant species.Communications chemistry · 2025Article
- cGAS/STING signalling pathway in senescence and oncogenesis.Seminars in cancer biology · 2024Review
- Identification of the extracellular membrane protein ENPP3 as a major cGAMP hydrolase and innate immune checkpoint.Cell reports · 2024Article
- RECQL4 Inhibits Radiation-Induced Tumor Immune Awakening via Suppressing the cGAS-STING Pathway in Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Dysregulation of the cGAS-STING Pathway in Monogenic Autoinflammation and Lupus.Frontiers in immunology · 2022Review
- Effect of radiotherapy on T cell and PD-1 / PD-L1 blocking therapy in tumor microenvironment.Human vaccines & immunotherapeutics · 2021Review
- A Luminescence-Based Coupled Enzyme Assay Enables High-Throughput Quantification of the Bacterial Second Messenger 3'3'-Cyclic-Di-AMP.Chembiochem : a European journal of chemical biology · 2021Article
- A STING-based fluorescent polarization assay for monitoring activities of cyclic dinucleotide metabolizing enzymes.RSC chemical biology · 2021Article
- DNA Sensing in Mismatch Repair-Deficient Tumor Cells Is Essential for Anti-tumor Immunity.Cancer cell · 2021Article
- Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase (cGAS), a Multifaceted Platform of Intracellular DNA Sensing.Frontiers in immunology · 2021Review
- Regulation and inhibition of the DNA sensor cGAS.EMBO reports · 2020Review
- Structure-Aided Development of Small-Molecule Inhibitors of ENPP1, the Extracellular Phosphodiesterase of the Immunotransmitter cGAMP.Cell chemical biology · 2020Article
- LRRC8A:C/E Heteromeric Channels Are Ubiquitous Transporters of cGAMP.Molecular cell · 2020Article
- A STING-based biosensor affords broad cyclic dinucleotide detection within single living eukaryotic cells.Nature communications · 2020Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
2',5'/3',5'-cGMP-AMP (cGAMP) is a second messenger produced in response to cytosolic dsDNA that activates the stimulator of interferon genes (STING) pathway. We recently discovered that cGAMP is exported by cancer cells and that this extracellular signal is an immunotransmitter key to tumor detection and elimination by the innate immune system. The enhancement of extracellular cGAMP levels therefore holds great promise for managing cancer. However, there is still much more to understand about the basic biology of cGAMP before its full therapeutic potential can be realized. To answer these questions, we must be able to detect and quantitate cGAMP with an assay that is high-throughput, sensitive, and precise. Existing assays fall short of these needs. Here, we describe the development of cGAMP-Luc, a coupled enzyme assay that relies on the degradation of cGAMP to AMP by ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) and an optimized assay for the detection of AMP by luciferase. We also developed STING-CAP, a STING-mediated method to concentrate and purify cGAMP from any type of biological sample. We conclude that cGAMP-Luc is an economical high-throughput assay that matches the accuracy of and surpasses the detection limit of MS, the current gold standard of cGAMP quantitation. We propose that cGAMP-Luc is a powerful tool that may enable discoveries that advance insights into extracellular cGAMP levels in healthy and diseased tissues, such as cancer.
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