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Ceftazidime reduces cellular Skp2 to promote type-I interferon activity
Caixia Qiao1, Fan Huang1,2, Jiuyi He1
1Institutes of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, Jiangsu, China.
Immunology
|August 29, 2023
Summary
Skp2 protein promotes viral infections by degrading the type-I interferon receptor (IFNAR2). The antibiotic ceftazidime inhibits Skp2, enhancing antiviral defenses.
Area of Science:
- Immunology
- Molecular Biology
- Virology
Background:
- Skp2 is implicated in various cellular processes and cancer.
- Type-I interferons (IFN-I) are crucial for antiviral immunity.
- The regulation of IFN-I signaling by Skp2 remains largely unexplored.
Purpose of the Study:
- To investigate the role of Skp2 in IFN-I-mediated antiviral activity.
- To identify mechanisms by which Skp2 affects IFN-I signaling.
- To explore potential therapeutic strategies targeting Skp2 for antiviral purposes.
Main Methods:
- Cell-based assays to assess viral infection and IFN-I signaling.
- Co-immunoprecipitation to study protein-protein interactions.
- Western blotting and ubiquitination assays to analyze protein degradation.
- Treatment with ceftazidime to evaluate its effect on Skp2 and IFN-I activity.
Main Results:
- Skp2 was found to promote viral infection.
- Skp2 interacts with IFNAR2 and promotes its K48-linked polyubiquitination and degradation.
- Skp2-mediated downregulation of IFNAR2 inhibits IFN-I signaling and antiviral responses.
- Ceftazidime was identified as a novel repressor of Skp2.
- Ceftazidime treatment enhanced IFNAR2 stability and IFN-I antiviral activity.
Conclusions:
- Skp2 negatively regulates IFN-I-mediated antiviral activity by targeting IFNAR2 for degradation.
- Ceftazidime emerges as a potential therapeutic agent to boost antiviral immunity by inhibiting Skp2.
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