ArticleImmunology2021
Cytoplasmic-translocated Ku70 senses intracellular DNA and mediates interferon-lambda1 induction.
Article in Immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 30 citations in OpenAlex.
- Cytoplasmic relocation of nuclear Ku70 by Bruceine A augments cGAS-STING pathway-mediated anti-tumor immunity.Acta pharmaceutica Sinica. B · 2026Article
- Repositioning Ku70 unlocks cGAS-STING immunity in colorectal cancer.Acta pharmaceutica Sinica. B · 2026Article
- STING agonists as antiviral agents.FEBS letters · 2026Review
- Nuclear Fraction Proteome Analyses During rAAV Production of AAV2-Plasmid-Transfected HEK-293 Cells.International journal of molecular sciences · 2025Article
- Nuclear VPS35 attenuates NHEJ repair by sequestering Ku protein.Molecular medicine (Cambridge, Mass.) · 2025Article
- Catch me if you can: viral nucleic acids to host sensors.Frontiers in immunology · 2025Review
- Ku70 silencing aggravates oxygen-glucose deprivation/reperfusion-induced injury by activation of the p53 apoptotic pathway in rat cortical astrocytes.Histochemistry and cell biology · 2024Article
- When DNA-damage responses meet innate and adaptive immunity.Cellular and molecular life sciences : CMLS · 2024Review
- Ku70 senses cytosolic DNA and assembles a tumor-suppressive signalosome.Science advances · 2024Article
- Cytosolic DNA sensors activation of human astrocytes inhibits herpes simplex virus through IRF1 induction.Frontiers in cellular and infection microbiology · 2024Article
- Interferon lambda in respiratory viral infection: immunomodulatory functions and antiviral effects in epithelium.Frontiers in immunology · 2024Review
- IFNλ1 is a STING-dependent mediator of DNA damage and induces immune activation in lung cancer.Frontiers in immunology · 2024Article
- (-)-Epigallocatechin-3-gallate induced apoptosis by dissociation of c-FLIP/Ku70 complex in gastric cancer cells.Journal of cellular and molecular medicine · 2023Article
- SMYD2 inhibition-mediated hypomethylation of Ku70 contributes to impaired nonhomologous end joining repair and antitumor immunity.Science advances · 2023Article
- Interferon-lambda: New role in intestinal symptoms of COVID-19.World journal of gastroenterology · 2023Review
- Interferon and autoantigens: intersection in autoimmunity.Frontiers in medicine · 2023Review
- Cytoplasmic DNAs: Sources, sensing, and roles in the development of lung inflammatory diseases and cancer.Frontiers in immunology · 2023Review
- STING signaling in inflammaging: a new target against musculoskeletal diseases.Frontiers in immunology · 2023Review
- Manganese enhances DNA- or RNA-mediated innate immune response by inducing phosphorylation of TANK-binding kinase 1.iScience · 2022Article
- Roles of RNA Sensors in Host Innate Response to Influenza Virus and Coronavirus Infections.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
We have previously identified that human Ku70, a nuclear protein, serves as a cytosolic DNA sensor. Upon transfection with DNA or infection with DNA virus, Ku70 translocates from the nucleus into the cytoplasm and then predominately induces interferon lambda1 (IFN-λ1) rather than IFN-alpha or IFN-beta, through a STING-dependent signalling pathway. However, a detailed mechanism for Ku70 cytoplasmic translocation and its correlation with IFN-λ1 induction have not been fully elucidated. Here, we observed that cytoplasmic translocation of Ku70 only occurred in DNA-triggered IFN-λ1-inducible cells. Additionally, infection by Herpes simplex virus type-1 (HSV-1), a DNA virus, induces cytoplasmic translocation of Ku70 and IFN-λ1 induction in a strain-dependent manner: the translocation and IFN-λ1 induction were detected upon infection by HSV-1 McKrae, but not MacIntyre, strain. A kinetic analysis indicated that cytoplasmic translocation of Ku70 was initiated right after DNA transfection and was peaked at 6 hr after DNA stimulation. Furthermore, treatment with leptomycin B, a nuclear export inhibitor, inhibited both Ku70 translocation and IFN-λ1 induction, suggesting that Ku70 translocation is an essential and early event for its cytosolic DNA sensing. We further confirmed that enhancing the acetylation status of the cells promotes Ku70's cytoplasmic accumulation, and therefore increases DNA-mediated IFN-λ1 induction. These findings provide insights into the molecular mechanism by which the versatile sensor detects pathogenic DNA in a localization-dependent manner.
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