Related Experiment Video

Updated: May 6, 2026

Monitoring Activation of the Antiviral Pattern Recognition Receptors RIG-I And PKR By Limited Protease Digestion and Native PAGE
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Monitoring Activation of the Antiviral Pattern Recognition Receptors RIG-I And PKR By Limited Protease Digestion and Native PAGE

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The USP43/RNF2 axis negatively regulates antiviral innate immunity by promoting TBK1 ubiquitination and degradation

Xibao Zhao1, Qianqian Di1, Jin Chen1

  • 1Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Marshall Laboratory of Biomedical Engineering, Institute of Biological Therapy, Shenzhen University Medical School, Shenzhen University, Shenzhen, China.

Cell Death and Differentiation
|March 28, 2025
PubMed

Insights

Ubiquitin specific peptidase 43 (USP43) stabilizes ring finger protein 2 (RNF2), enhancing antiviral immunity by regulating TBK1 degradation. This reveals a novel USP43/RNF2 pathway in innate immune response.

Area of Science:

  • Cellular Biology
  • Immunology
  • Biochemistry

Background:

  • E3 ubiquitin ligases control protein degradation, but their own regulation is unclear.
  • Understanding E3 ligase stability is crucial for cellular processes and disease.

Purpose of the Study:

  • To investigate the post-translational modification and stability of the E3 ubiquitin ligase RNF2.
  • To elucidate the role of USP43 in regulating RNF2 and its impact on antiviral immunity.

Main Methods:

  • Interactome and quantitative ubiquitinome mass spectrometry.
  • In vitro and in vivo studies using VSV infection models.
  • Analysis of ubiquitination and protein degradation pathways.

Main Results:

  • USP43 deubiquitinates and stabilizes RNF2 by removing K48-linked ubiquitination.
  • USP43 negatively regulates type I interferon expression, enhancing antiviral immunity in USP43-deficient cells.
  • RNF2 promotes TBK1 degradation via K48-linked ubiquitination, a process influenced by USP43.

Conclusions:

  • USP43 stabilizes RNF2, revealing a novel mechanism for E3 ligase stability.
  • The USP43/RNF2 axis plays a critical role in regulating antiviral innate immunity.
  • This pathway offers potential targets for modulating immune responses.

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