2020 Fiscal Year Annual Research Report
Unveiling Novel STAT1 Activation Expands its Anti-viral Role into Host Defense Against Bacterial Pathogens
| Project/Area Number |
19K23864
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| Research Institution | Osaka University |
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Principal Investigator |
METWALLY HOZAIFA 大阪大学, 免疫学フロンティア研究センター, 特任研究員 (40844246)
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| Project Period (FY) |
2019-08-30 – 2021-03-31
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| Keywords | Threonine / phosphorylation / STAT1 / TLR4 / cytokines |
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| Outline of Annual Research Achievements |
Signal transducer and activator of transcription 1 (STAT1) regulates a wide-range of biological processes. Tyr701 phosphorylation of STAT1 signaling cascade is well known for its essential role in mediating cellular responses to interferons (IFN) such as antiviral response. However, Tyr701 phosphorylation cannot explain the full spectrum of STAT1 activities, especially in the context of bacterial infections and inflammation. Our study unraveled an endosomal-originated noncanonical signaling resulting in a noncanonical Thr749 phosphorylation, which confers STAT1 with distinct DNA binding and proinflammatory gene-regulatory properties in response to TLR4 stimulation. Our findings adds a dynamic dimension to the current working paradigm of STAT1 that may apply to other STAT family proteins.
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