%0 Journal Article
%A Acharya, Dhiraj
%A Sayyad, Zuberwasim
%A Hoenigsperger, Helene
%A Hirschenberger, Maximilian
%A Zurenski, Matthew
%A Balakrishnan, Kannan
%A Zhu, Junji
%A Gableske, Sebastian
%A Kato, Jiro
%A Zhang, Shen-Ying
%A Casanova, Jean-Laurent
%A Moss, Joel
%A Sparrer, Konstantin M J
%A Gack, Michaela U
%T TRIM23 mediates cGAS-induced autophagy in anti-HSV defense.
%J Nature Communications
%V 16
%N 1
%@ 2041-1723
%C [London]
%I Springer Nature
%M DZNE-2025-00610
%P 4418
%D 2025
%X The cGAS-STING pathway, well-known to elicit interferon (IFN) responses, is also a key inducer of autophagy upon virus infection or other stimuli. Whereas the mediators for cGAS-induced IFN responses are well characterized, much less is known about how cGAS elicits autophagy. Here, we report that TRIM23, a unique TRIM protein harboring both ubiquitin E3 ligase and GTPase activity, is crucial for cGAS-STING-dependent antiviral autophagy. Genetic ablation of TRIM23 impairs autophagic control of HSV-1 infection. HSV-1 infection or cGAS-STING stimulation induces TBK1-mediated TRIM23 phosphorylation at S39, which triggers TRIM23 autoubiquitination and GTPase activity and ultimately elicits autophagy. Fibroblasts from a patient with herpes simplex encephalitis heterozygous for a dominant-negative, kinase-inactivating TBK1 mutation fail to activate autophagy by TRIM23 and cGAS-STING. Our results thus identify the cGAS-STING-TBK1-TRIM23 axis as a key autophagy defense pathway and may stimulate new therapeutic interventions for viral or inflammatory diseases.
%K Autophagy: immunology
%K Humans
%K Nucleotidyltransferases: metabolism
%K Nucleotidyltransferases: genetics
%K Nucleotidyltransferases: immunology
%K Herpesvirus 1, Human: immunology
%K Herpesvirus 1, Human: physiology
%K Protein Serine-Threonine Kinases: metabolism
%K Protein Serine-Threonine Kinases: genetics
%K Membrane Proteins: metabolism
%K Membrane Proteins: genetics
%K Animals
%K Phosphorylation
%K Fibroblasts: metabolism
%K Fibroblasts: virology
%K Mice
%K Ubiquitin-Protein Ligases: metabolism
%K Ubiquitin-Protein Ligases: genetics
%K Herpes Simplex: immunology
%K Herpes Simplex: virology
%K HEK293 Cells
%K Signal Transduction
%K Ubiquitination
%K Nucleotidyltransferases (NLM Chemicals)
%K Protein Serine-Threonine Kinases (NLM Chemicals)
%K Membrane Proteins (NLM Chemicals)
%K cGAS protein, human (NLM Chemicals)
%K TBK1 protein, human (NLM Chemicals)
%K STING1 protein, human (NLM Chemicals)
%K Ubiquitin-Protein Ligases (NLM Chemicals)
%K cGAS protein, mouse (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40360474
%2 pmc:PMC12075517
%R 10.1038/s41467-025-59338-5
%U https://pub.dzne.de/record/278654