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KAT5 acetylates cGAS to promote innate immune response to DNA virus
- Source :
- Proc Natl Acad Sci U S A
- Publication Year :
- 2020
- Publisher :
- Proceedings of the National Academy of Sciences, 2020.
-
Abstract
- The DNA sensor cGMP-AMP synthase (cGAS) senses cytosolic microbial or self DNA to initiate a MITA/STING-dependent innate immune response. cGAS is regulated by various posttranslational modifications at its C-terminal catalytic domain. Whether and how its N-terminal unstructured domain is regulated by posttranslational modifications remain unknown. We identified the acetyltransferase KAT5 as a positive regulator of cGAS-mediated innate immune signaling. Overexpression of KAT5 potentiated viral-DNA–triggered transcription of downstream antiviral genes, whereas a KAT5 deficiency had the opposite effects. Mice with inactivated Kat5 exhibited lower levels of serum cytokines in response to DNA virus infection, higher viral titers in the brains, and more susceptibility to DNA-virus–induced death. Mechanistically, KAT5 catalyzed acetylation of cGAS at multiple lysine residues in its N-terminal domain, which promoted its DNA-binding ability. Our findings suggest that KAT5-mediated cGAS acetylation at its N terminus is important for efficient innate immune response to DNA virus.
- Subjects :
- Male
Biology
Lysine Acetyltransferase 5
Mice
Viral Proteins
chemistry.chemical_compound
Transcription (biology)
Animals
Humans
KAT5
Cyclic GMP
Gene
Mice, Knockout
Multidisciplinary
Innate immune system
DNA Viruses
Acetylation
DNA virus
Interferon-beta
Biological Sciences
Nucleotidyltransferases
DNA Virus Infections
Immunity, Innate
Cell biology
HEK293 Cells
chemistry
Acetyltransferase
Host-Pathogen Interactions
Female
Nitric Oxide Synthase
Protein Processing, Post-Translational
DNA
HeLa Cells
Signal Transduction
Subjects
Details
- ISSN :
- 10916490 and 00278424
- Volume :
- 117
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences
- Accession number :
- edsair.doi.dedup.....678744bdfd2957770d699b203e65bbd7