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| Main Authors: | , , , , , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
Cell reports
2026
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/41520336/ |
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| _version_ | 1868266100239630337 |
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| author | Deng, Hongyan Jia, Shuke Zhu, Chunchun Hua, Jiale Wang, Zixuan Sun, Xueyi Liu, Wen Shi, Liyun Li, Wenhua Gui, Jian-Fang Liu, Xing Xiao, Wuhan |
| author_facet | Deng, Hongyan Jia, Shuke Zhu, Chunchun Hua, Jiale Wang, Zixuan Sun, Xueyi Liu, Wen Shi, Liyun Li, Wenhua Gui, Jian-Fang Liu, Xing Xiao, Wuhan Deng, Hongyan Jia, Shuke Zhu, Chunchun Hua, Jiale Wang, Zixuan Sun, Xueyi Liu, Wen Shi, Liyun Li, Wenhua Gui, Jian-Fang Liu, Xing Xiao, Wuhan |
| collection | PubMed - marine biology |
| contents | IRF3 attenuates hypoxia signaling by retaining HIF-α in the cytoplasm. Deng, Hongyan Jia, Shuke Zhu, Chunchun Hua, Jiale Wang, Zixuan Sun, Xueyi Liu, Wen Shi, Liyun Li, Wenhua Gui, Jian-Fang Liu, Xing Xiao, Wuhan Animals Hypoxia-Inducible Factor 1, alpha Subunit Signal Transduction Cytoplasm Interferon Regulatory Factor-3 Basic Helix-Loop-Helix Proteins Endothelial PAS Domain-Containing Protein 1 Mice Zebrafish Cell Hypoxia Humans HEK293 Cells 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. |
| format | Artículo científico |
| id | pubmed_41520336 |
| institution | PubMed |
| language | en |
| publishDate | 2026 |
| publisher | Cell reports |
| record_format | pubmed |
| spellingShingle | IRF3 attenuates hypoxia signaling by retaining HIF-α in the cytoplasm. Deng, Hongyan Jia, Shuke Zhu, Chunchun Hua, Jiale Wang, Zixuan Sun, Xueyi Liu, Wen Shi, Liyun Li, Wenhua Gui, Jian-Fang Liu, Xing Xiao, Wuhan Animals Hypoxia-Inducible Factor 1, alpha Subunit Signal Transduction Cytoplasm Interferon Regulatory Factor-3 Basic Helix-Loop-Helix Proteins Endothelial PAS Domain-Containing Protein 1 Mice Zebrafish Cell Hypoxia Humans HEK293 Cells IRF3 attenuates hypoxia signaling by retaining HIF-α in the cytoplasm. Deng, Hongyan Jia, Shuke Zhu, Chunchun Hua, Jiale Wang, Zixuan Sun, Xueyi Liu, Wen Shi, Liyun Li, Wenhua Gui, Jian-Fang Liu, Xing Xiao, Wuhan Animals Hypoxia-Inducible Factor 1, alpha Subunit Signal Transduction Cytoplasm Interferon Regulatory Factor-3 Basic Helix-Loop-Helix Proteins Endothelial PAS Domain-Containing Protein 1 Mice Zebrafish Cell Hypoxia Humans HEK293 Cells 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. |
| title | IRF3 attenuates hypoxia signaling by retaining HIF-α in the cytoplasm. |
| topic | Animals Hypoxia-Inducible Factor 1, alpha Subunit Signal Transduction Cytoplasm Interferon Regulatory Factor-3 Basic Helix-Loop-Helix Proteins Endothelial PAS Domain-Containing Protein 1 Mice Zebrafish Cell Hypoxia Humans HEK293 Cells |
| url | https://pubmed.ncbi.nlm.nih.gov/41520336/ |