ArticleThe Journal of experimental medicine2023
Deficiency for SAMHD1 activates MDA5 in a cGAS/STING-dependent manner.
Article in The Journal of experimental medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
- Cyclosporin A triggers a RIG-I-mediated interferon response through multiple cellular processes.Scientific reports · 2026Article
- BRCA1 deficiency induces NFκB-dependent type-I interferon signaling in fallopian tube epithelial cells.Neoplasia (New York, N.Y.) · 2026Article
- SAMHD1 depletion restricts SARS-CoV-2 infection by suppressing HNF1-dependent ACE2 expression in lung epithelial cells.PLoS pathogens · 2026Article
- Nucleotide metabolic rewiring enables NLRP3 inflammasome hyperactivation in obesity.Science (New York, N.Y.) · 2026Article
- A homozygous splice-site variant in SAMHD1 shows variable expressivity of Aicardi-Goutières syndrome type 5: a case report and literature review.Frontiers in pediatrics · 2026Article
- Impact of SAMHD1 and phosphorylated ATM levels on the progression and prognosis of patients with soft tissue sarcoma.Oncology letters · 2025Article
- Genome instability and crosstalk with the immune response.Genome medicine · 2025Review
- SAMHD1 promotes SARS-CoV-2 infection by enhancing HNF1-dependent ACE2 expression in lung epithelial cells.bioRxiv : the preprint server for biology · 2025Article
- Mouse models of type I interferonopathies.Human molecular genetics · 2025Review
- Autocrine interferon poisoning mediates ADAR1-dependent synthetic lethality in BRCA1/2-mutant cancers.Nature communications · 2025Article
- A 33-year diagnostic odyssey in an Ashkenazi Jewish patient with Aicardi-Goutières syndrome.The journal of allergy and clinical immunology. Global · 2025Article
- Decoding Immunobiology Through Genetic Errors of Immunity.Annual review of immunology · 2025Review
- Nucleic acid triggers of autoimmunity and autoinflammation.Current opinion in immunology · 2025Review
- Cytosolic nucleic acid sensing as driver of critical illness: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2025Review
- Nuclear Overexpression of SAMHD1 Induces M Phase Stalling in Hepatoma Cells and Suppresses HCC Progression by Interacting with the Cohesin Complex.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- EFTUD2 is a promising diagnostic and prognostic indicator involved in the tumor immune microenvironment and glycolysis of lung adenocarcinoma.Frontiers in oncology · 2025Article
- IRF6 Enhances IFN-β Expression and Inhibits Viral Replication to Reduce the Severity of Herpetic Stromal Keratitis.Journal of inflammation research · 2025Article
- Deciphering the role of SAMHD1 in endometrial cancer progression.Biology direct · 2024Article
- The prototypical interferonopathy: Aicardi-Goutières syndrome from bedside to bench.Immunological reviews · 2024Review
- Review
Corrections and comments
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Authors and funding
31 authors at 9 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Defects in nucleic acid metabolizing enzymes can lead to spontaneous but selective activation of either cGAS/STING or RIG-like receptor (RLR) signaling, causing type I interferon-driven inflammatory diseases. In these pathophysiological conditions, activation of the DNA sensor cGAS and IFN production are linked to spontaneous DNA damage. Physiological, or tonic, IFN signaling on the other hand is essential to functionally prime nucleic acid sensing pathways. Here, we show that low-level chronic DNA damage in mice lacking the Aicardi-Goutières syndrome gene SAMHD1 reduced tumor-free survival when crossed to a p53-deficient, but not to a DNA mismatch repair-deficient background. Increased DNA damage did not result in higher levels of type I interferon. Instead, we found that the chronic interferon response in SAMHD1-deficient mice was driven by the MDA5/MAVS pathway but required functional priming through the cGAS/STING pathway. Our work positions cGAS/STING upstream of tonic IFN signaling in Samhd1-deficient mice and highlights an important role of the pathway in physiological and pathophysiological innate immune priming.
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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.