Year: 2026
Type: article
Abstract: Interferon regulatory factor 3 (IRF3) functions as a key transcription factor in the innate antiviral immune response, which depends on its nuclear localization. However, its function in the cytoplasm during non-infection states remains largely unknown. In this study, we found that resting cytoplasmic IRF3 interacts with hypoxia-inducible factor (HIF)-1α and HIF-2α, two master regulators of hypoxia signaling. This interaction retains HIF-α in the cytoplasm under hypoxic conditions, preventing it from exerting its transcription factor function and attenuating hypoxia signaling. Disruption of IRF3 in both mice and zebrafish resulted in increased expression of hypoxia response genes and enhanced tolerance to hypoxia. These findings suggest that, in the absence of viral infection, cytoplasmic IRF3 modulates hypoxia signaling by retaining HIF-α in the cytoplasm under hypoxic conditions.
Source: Cell Reports
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,620
Funders: U.S. Department of Energy, Deutsche Forschungsgemeinschaft, National Natural Science Foundation of China, Chinese Academy of Sciences, China Postdoctoral Science Foundation, Natural Science Foundation of Hubei Province, National Institutes of Health, Office of Science, National Key Research and Development Program of China, National Cancer Institute, National Institute of General Medical Sciences, Argonne National Laboratory
Awards: G102163711, G107546177, G1313983767, G1664757510, G1982118090, G2164036156, G2287611682, G2397766651, G262962599, G3075337988, G3407338877, Structure and function in Notch Signaling, G3479632140, G3548664411, G4088091130, G409777406, G498139845, G5384392517, G5607048534, G5644180676, G666778509, G6848031779, G6848963361, G6918803902, G7382435089, NE-CAT Center for Advanced Macromolecular Crystallography, G9000038451, G9000056318, G9000084495, G9000119994, G9000318139, G969889393, G993149817
OpenAlex ID: W7121627029