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2020 Fiscal Year Annual Research Report

Unveiling Novel STAT1 Activation Expands its Anti-viral Role into Host Defense Against Bacterial Pathogens

Research Project

Project/Area Number 19K23864
Research InstitutionOsaka University

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)

Project Period (FY) 2019-08-30 – 2021-03-31
KeywordsThreonine / phosphorylation / STAT1 / TLR4 / cytokines
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.

Research Products

(4 results)

All 2020

All Journal Article (4 results)

  • [Journal Article] Distinct Phosphorylation of STAT1 Confers Distinct DNA Binding and Gene-regulatory Properties2020

    • Author(s)
      Metwally Hozaifa、Kishimoto Tadamitsu
    • Journal Title

      Journal of Cellular Signaling

      Volume: 1 Pages: .

    • DOI

      10.33696/Signaling.1.012

  • [Journal Article] The Yin and the Yang of STAT1 Downstream of TLR4 Endocytosis: STAT1 beyond Interferon Signaling2020

    • Author(s)
      Metwally Hozaifa、Kishimoto Tadamitsu
    • Journal Title

      Journal of Cellular Immunology

      Volume: 2 Pages: .

    • DOI

      10.33696/immunology.2.044

  • [Journal Article] Historical overview of the interleukin-6 family cytokine2020

    • Author(s)
      Kang Sujin、Narazaki Masashi、Metwally Hozaifa、Kishimoto Tadamitsu
    • Journal Title

      Journal of Experimental Medicine

      Volume: 217 Pages: .

    • DOI

      10.1084/jem.20190347

  • [Journal Article] Noncanonical STAT1 phosphorylation expands its transcriptional activity into promoting LPS-induced IL-6 and IL-12p40 production2020

    • Author(s)
      Metwally Hozaifa、Tanaka Toshio、Li Songling、Parajuli Gyanu、Kang Sujin、Hanieh Hamza、Hashimoto Shigeru、Chalise Jaya P.、Gemechu Yohannes、Standley Daron M.、Kishimoto Tadamitsu
    • Journal Title

      Science Signaling

      Volume: 13 Pages: .

    • DOI

      10.1126/scisignal.aay0574

URL: 

Published: 2021-12-27  

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