ArticleMolecular cell2015
Ancient Origin of cGAS-STING Reveals Mechanism of Universal 2',3' cGAMP Signaling.
Article in Molecular cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 papers, 1 of them a synthesis that pooled it.
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Who cites it
153 citing papers in PubMed, 1 synthesis or guideline pooled it, 247 citations in OpenAlex.
- Molecular mechanisms and therapeutic strategies of cGAS-STING pathway in liver disease: the quest continues.Frontiers in immunology · 2025Pooled it
- Is a Commensal Here, a Pathogen There? Genotype Specific Responses by the Sea Anemone Nematostella vectensis to Vibrio Species.Molecular ecology · 2026Article
- DNA Sensing and Neuroinflammation: Mechanistic Insights into cGAS-STING Biology and Therapeutic Translation in Age-Related Neurodegenerative Diseases.Molecular neurobiology · 2026Review
- Stimulator of interferon genes (STING) in renal tumors: Biological bases, diagnostic relevance, and predictive potential.Histology and histopathology · 2026Review
- Functional diversity of phage sponge proteins that sequester host immune signals.Nature microbiology · 2026Article
- Expanding roles of cGAS-STING signaling in neuroinflammation.The Journal of clinical investigation · 2026Review
- FADD is recruited to activated STING oligomers to initiate caspase-mediated NF-κB activation in Drosophila melanogaster.The EMBO journal · 2026Article
- A unique Z-shaped tetramer mediates the autoinhibition of waterfowl STING.PLoS pathogens · 2026Article
- A biomimetic nanodisc system selectively activates type I interferons by nonclassical STING pathway for cancer immunotherapy.Nature communications · 2026Article
- Manipulation of the nucleotide pool in human, bacterial and plant immunity.Nature reviews. Immunology · 2026Review
- Targeting pattern recognition receptors for cancer therapy: Mechanisms and strategies.Acta pharmaceutica Sinica. B · 2025Review
- Beyond tumour suppression: cGAS-STING pathway in urologic malignancies: Context-dependent duality and therapeutic implications.Clinical and translational medicine · 2025Review
- Advances in nanomaterials for enhancing cGAS-STING pathway mediated anti-tumor treatment.Materials today. Bio · 2025Review
- Beyond interferons: Non-canonical roles of MITA/STING.Cell insight · 2025Review
- A choanoflagellate cGLR-STING pathway reveals evolutionary links between bacterial and animal immunity.bioRxiv : the preprint server for biology · 2025Article
- Defining STING-sterol interactions with chemoproteomics.RSC chemical biology · 2025Article
- Orthosteric STING inhibition elucidates molecular correction of SAVI STING.Nature communications · 2025Article
- cGAS-STING: mechanisms and therapeutic opportunities.Science China. Life sciences · 2025Review
- Antiviral Mx proteins have an ancient origin and widespread distribution among eukaryotes.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Oxymatrine, a novel TLR2 agonist, promotes megakaryopoiesis and thrombopoiesis through the STING/NF-κB pathway.Journal of pharmaceutical analysis · 2025Article
93 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
In humans, the cGAS-STING immunity pathway signals in response to cytosolic DNA via 2',3' cGAMP, a cyclic dinucleotide (CDN) second messenger containing mixed 2'-5' and 3'-5' phosphodiester bonds. Prokaryotes also produce CDNs, but these are exclusively 3' linked, and thus the evolutionary origins of human 2',3' cGAMP signaling are unknown. Here we illuminate the ancient origins of human cGAMP signaling by discovery of a functional cGAS-STING pathway in Nematostella vectensis, an anemone species >500 million years diverged from humans. Anemone cGAS appears to produce a 3',3' CDN that anemone STING recognizes through nucleobase-specific contacts not observed in human STING. Nevertheless, anemone STING binds mixed-linkage 2',3' cGAMP indistinguishably from human STING, trapping a unique structural conformation not induced by 3',3' CDNs. These results reveal that human mixed-linkage cGAMP achieves universal signaling by exploiting a deeply conserved STING conformational intermediate, providing critical insight for therapeutic targeting of the STING 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.