ArticleEMBO reports2023
XAF1 prevents hyperproduction of type I interferon upon viral infection by targeting IRF7.
Article in EMBO reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- CD160Cellular & molecular immunology · 2026Article
- Matrix and intermembrane space-specific mitochondrial stress response in Alzheimer's disease.NPJ dementia · 2026Article
- Immune dysregulation in COVID-19 induced ARDS in kidney transplant recipients revealed by single-cell RNA sequencing.Scientific reports · 2025Article
- Article
- De novo variants in immune regulatory genes in Down syndrome regression disorder.Journal of neurology · 2024Article
- XAF1 promotes osteoclast apoptosis by antagonizing the XIAP-caspase axis.Journal of orthopaedic translation · 2024Article
- Comparative Study on the Mechanism of Macrophage Activation Induced by Polysaccharides from Fresh and Dried Longan.Nutrients · 2024Article
- XAF1 promotes colorectal cancer metastasis via VCP-RNF114-JUP axis.The Journal of cell biology · 2024Article
- Neuronal-specific TNFAIP1 ablation attenuates postoperative cognitive dysfunction via targeting SNAP25 for K48-linked ubiquitination.Cell communication and signaling : CCS · 2023Article
- XAF1 prevents hyperproduction of type I interferon upon viral infection by targeting IRF7.EMBO reports · 2023Article
- IRF7: role and regulation in immunity and autoimmunity.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interferon regulatory factor (IRF) 3 and IRF7 are master regulators of type I interferon (IFN-I)-dependent antiviral innate immunity. Upon viral infection, a positive feedback loop is formed, wherein IRF7 promotes further induction of IFN-I in the later stage. Thus, it is critical to maintain a suitably low level of IRF7 to avoid the hyperproduction of IFN-I. In this study, we find that early expression of IFN-I-dependent STAT1 promotes the expression of XAF1 and that XAF1 is associated specifically with IRF7 and inhibits the activity of XIAP. XAF1-knockout and XIAP-transgenic mice display resistance to viral infection, and this resistance is accompanied by increases in IFN-I production and IRF7 stability. Mechanistically, we find that the XAF1-XIAP axis controls the activity of KLHL22, an adaptor of the BTB-CUL3-RBX1 E3 ligase complex through a ubiquitin-dependent pathway. CUL3-KLHL22 directly targets IRF7 and catalyzes its K48-linked ubiquitination and proteasomal degradation. These findings reveal unexpected functions of the XAF1-XIAP axis and KLHL22 in the regulation of IRF7 stability and highlight an important target for antiviral innate immunity.
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