Skip to content
DraconiticResearch
Search Sources API
203,234 studies31 sourcesUpdated 5 min ago
Peer-reviewedCC BY 4.0PLOS Pathogens

MARK3 promotes host antiviral defense by driving GEF-H1–mediated TBK1 activation

  • Xingmei Qi1
  • Xue Zhu1
  • Wenbiao Peng2,3,4
  • Luoxue Hua2,3,4
  • Xinru Xie3,4
  • Chuncan Si5
  • Meimei Lan2
  • Zifan Zhuang2
  • Siyi Ding2
  • Ting Xu2
  • Junjie Li2
  • Yundi Zhang2
6 more authors
  • Yifan Song2
  • Yiping Yang2
  • Yixue Cheng2
  • Tao Guo3,4
  • Linchao Li2,3,4
  • Kezhen Wang2,3,4
5 affiliations
  1. 1Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu, China
  2. 2Department of Microbiology and Biotechnology, College of Life Sciences, Anhui Medical University, Hefei, China
  3. 3Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
  4. 4Anhui Public Health Clinical Center, Hefei, China
  5. 5School of Biological and Environmental Engineering, Jingdezhen University, Jingdezhen, China
Read full textPDFDOICite

Abstract

Innate immunity constitutes the body’s first line of defense against pathogenic challenge, serving not only as a physical and cellular bulwark that rapidly curbs microbial proliferation but also as the essential rheostat that orchestrates downstream adaptive immune responses. Here, we identified MARK3, a serine/threonine protein kinase of the conserved MARK family, as a crucial regulator of innate antiviral immunity that promotes type I interferon (IFN-I) production in a kinase-dependent manner. Using both in vitro and in vivo models, we demonstrate that MARK3 exerts broad-spectrum antiviral activity via a signaling axis involving GEF-H1 and TBK1. Mechanistically, MARK3 directly interacts with GEF-H1 and phosphorylates it at Ser645. This phosphorylation event potentiates the activation of TBK1, leading to enhanced IRF3 phosphorylation. Activated IRF3 then translocates to the nucleus, where it triggers potent IFN-I induction and the downstream expression of interferon-stimulated genes (ISGs). Our study establishes MARK3 as an important antiviral kinase and defines the MARK3–GEF-H1–TBK1 axis as a novel signaling pathway driving interferon-mediated antiviral defense. Author summary: The innate immune system serves as the body’s first line of defense against viral pathogens, acting to curb infection at its earliest stages. In this study, we identified MARK3 as a candidate GEF-H1–interacting kinase and further showed that it enhances innate antiviral immunity in a kinase-dependent manner. Using both in vitro and in vivo models, we demonstrate that MARK3 binds to and phosphorylates GEF-H1 at Ser645, which in turn promotes TBK1 and IRF3 phosphorylation, driving robust activation of type I interferons to reinforce the host antiviral response.

Related

  1. FAM50A promotes esophageal squamous cell carcinoma progression via splicing-dependent oncogenic circSDK1- and DUSP22-mediated MAPK/FAK activation.
    Yan Bian, Ye Gao, Xin Chang +7
    Cell discoveryPeer-reviewedCC BYFull textMolecular biology & gene regulationEurope PMCDOAJ
  2. Xiaoai Jiedu recipe promotes NLRP3 inflammasome activation by alleviating PINK1-mediated mitophagy in hepatocellular carcinoma
    Yuan-yuan Wu, Hui-ming Zhu, Zi-yu Lu +3
    Frontiers in OncologyPeer-reviewedCC BY 4.0Full textMolecular biology & gene regulationCrossref
  3. Nuclear Factor Kappa‐B Inducing Kinase‐ and Inhibitor of Nuclear Factor Kappa‐B Kinase Subunit Beta‐Binding Protein Promotes Pathological Cardiac Hypertrophy by Regulating Inhibitor of Nuclear Factor Kappa‐B Kinase Subunit Beta‐Mediated Nuclear Factor Kappa‐B Activation
    Zheng Xie, Yingjie Zuo, Mengyao Wang +11
    Journal of the American Heart AssociationPeer-reviewedCC BY-NC-NDMolecular biology & gene regulationCrossref
  4. Structural basis of assembly-dependent activation of the MAD3–MAD4 nuclease in the Pseudomonas aeruginosa MADS defense system
    Jin Zhang, Zengru Li, Le Ye +3
    Nucleic Acids ResearchPeer-reviewedCC BY-NC 4.0Full textMolecular biology & gene regulationCrossref
  5. Model-Guided Engineering of NS1-Truncated Influenza OP7 Particles with Enhanced Interferon-Mediated Antiviral Activity
    J. Piasecka, D. Ruediger, U. Reichl +1
    bioRxivPreprintCC BY-NCFull textMolecular biology & gene regulationbioRxiv

Cite

BibTeXRIS
BibTeX
@article{qi2026mark3,
  title = {{MARK3 promotes host antiviral defense by driving GEF-H1–mediated TBK1 activation}},
  author = {Xingmei Qi and Xue Zhu and Wenbiao Peng and Luoxue Hua and Xinru Xie and Chuncan Si and Meimei Lan and Zifan Zhuang and Siyi Ding and Ting Xu and Junjie Li and Yundi Zhang and Yifan Song and Yiping Yang and Yixue Cheng and Tao Guo and Linchao Li and Kezhen Wang},
  journal = {PLOS Pathogens},
  year = {2026},
  month = oct,
  doi = {10.1371/journal.ppat.1014701},
  url = {https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014701},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - MARK3 promotes host antiviral defense by driving GEF-H1–mediated TBK1 activation
AU  - Xingmei Qi
AU  - Xue Zhu
AU  - Wenbiao Peng
AU  - Luoxue Hua
AU  - Xinru Xie
AU  - Chuncan Si
AU  - Meimei Lan
AU  - Zifan Zhuang
AU  - Siyi Ding
AU  - Ting Xu
AU  - Junjie Li
AU  - Yundi Zhang
AU  - Yifan Song
AU  - Yiping Yang
AU  - Yixue Cheng
AU  - Tao Guo
AU  - Linchao Li
AU  - Kezhen Wang
PY  - 2026
DA  - 2026/10/27
JO  - PLOS Pathogens
DO  - 10.1371/journal.ppat.1014701
UR  - https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014701
AB  - Innate immunity constitutes the body’s first line of defense against pathogenic challenge, serving not only as a physical and cellular bulwark that rapidly curbs microbial proliferation but also as the essential rheostat that orchestrates downstream adaptive immune responses. Here, we identified MARK3, a serine/threonine protein kinase of the conserved MARK family, as a crucial regulator of innate antiviral immunity that promotes type I interferon (IFN-I) production in a kinase-dependent manner. Using both in vitro and in vivo models, we demonstrate that MARK3 exerts broad-spectrum antiviral activity via a signaling axis involving GEF-H1 and TBK1. Mechanistically, MARK3 directly interacts with GEF-H1 and phosphorylates it at Ser645. This phosphorylation event potentiates the activation of TBK1, leading to enhanced IRF3 phosphorylation. Activated IRF3 then translocates to the nucleus, where it triggers potent IFN-I induction and the downstream expression of interferon-stimulated genes (ISGs). Our study establishes MARK3 as an important antiviral kinase and defines the MARK3–GEF-H1–TBK1 axis as a novel signaling pathway driving interferon-mediated antiviral defense. Author summary: The innate immune system serves as the body’s first line of defense against viral pathogens, acting to curb infection at its earliest stages. In this study, we identified MARK3 as a candidate GEF-H1–interacting kinase and further showed that it enhances innate antiviral immunity in a kinase-dependent manner. Using both in vitro and in vivo models, we demonstrate that MARK3 binds to and phosphorylates GEF-H1 at Ser645, which in turn promotes TBK1 and IRF3 phosphorylation, driving robust activation of type I interferons to reinforce the host antiviral response.
SN  - 1553-7374
SN  - 1553-7366
ER  -