ArticleThe EMBO journal2022
ZDHHC18 negatively regulates cGAS-mediated innate immunity through palmitoylation.
Article in The EMBO journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 1 of them a synthesis that pooled it.
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Who cites it
74 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.
- cGAS in nucleus: The link between immune response and DNA damage repair.Frontiers in immunology · 2022Pooled it
- The cGAS-STING/MITA pathway in innate antiviral immunity and beyond.Cell insight · 2026Review
- Multi-Proteomic Insights into Lysine Propionylation and Malonylation Remodeling in PRRSV-Infected Porcine Lungs.Veterinary sciences · 2026Article
- ZDHHC5 may regulate the function of NKT cells and the immune response in Meniere's disease.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Article
- cGAS-STING as a Neuroimmune Traffic Molecule: Unraveling Pathogenic Mechanisms and Therapeutic Potential in Neurological Disorders.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026Review
- Palmitoylation-related gene signature for immune subtyping, prognostic stratification, and immunotherapy guidance in hepatocellular carcinoma.Translational cancer research · 2026Article
- Palmitic Acid Promotes Antiviral Innate Immunity via ZDHHC20-Mediated CMPK2 Palmitoylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Lactylation: a novel post-translational modification for cGAS-STING pathway.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Review
- Exploring the functional role of palmitoylation genes in clear cell renal cell carcinoma and their impact on tumor microenvironment.BMC genomic data · 2026Article
- ZDHHC5: a pivotal palmitoyltransferase orchestrating signaling networks - unraveling mechanisms and therapeutic horizons.Biomarker research · 2026Review
- ZDHHC11-mediated palmitoylation of viral envelope protein restricts dengue virus replication: implication for the development of universal anti-flavivirus therapeutic strategies.Virology journal · 2026Article
- ProteinJournal of pharmaceutical analysis · 2026Review
- Multi-omics analysis suggests ZDHHC18 as a potential risk factor for clear cell renal cell carcinoma linked to myeloid DC morphology.Discover oncology · 2026Article
- Opportunities and challenges of targeting cGAS-STING in cancer.Nature reviews. Cancer · 2026Review
- SIRT4 regulates antiviral and autoimmune responses by promoting cGAS-mediated signaling pathways.EMBO reports · 2026Article
- Anatid herpesvirus 1 UL51 protein is palmitoylated by DHHC9 and DHHC18 for viral replication and virulence.PLoS pathogens · 2026Article
- ZDHHC-Mediated Protein S-Palmitoylation in Cancer: Epigenetic Interfaces, Structural Logic and Therapeutic Targeting.International journal of medical sciences · 2026Review
- Article
- S-palmitoylation and depalmitoylation at the interface of animal virus-host interactions.Frontiers in cellular and infection microbiology · 2026Review
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Double-stranded DNA is recognized as a danger signal by cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS), triggering innate immune responses. Palmitoylation is an important post-translational modification (PTM) catalyzed by DHHC-palmitoyl transferases, which participate in the regulation of diverse biological processes. However, whether palmitoylation regulates cGAS function has not yet been explored. Here, we found that palmitoylation of cGAS at C474 restricted its enzymatic activity in the presence of double-stranded DNA. cGAS palmitoylation was catalyzed mainly by the palmitoyltransferase ZDHHC18 and double-stranded DNA promoted this modification. Mechanistically, palmitoylation of cGAS reduced the interaction between cGAS and double-stranded DNA, further inhibiting cGAS dimerization. Consistently, ZDHHC18 negatively regulated cGAS activation in human and mouse cell lines. In a more biologically relevant model system, Zdhhc18-deficient mice were found to be resistant to infection by DNA viruses, in agreement with the observation that ZDHHC18 negatively regulated cGAS mediated innate immune responses in human and mouse primary cells. In summary, the negative role of ZDHHC18-mediated cGAS palmitoylation may be a novel regulatory mechanism in the fine-tuning of innate immunity.
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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.