Ceftazidime reduces cellular Skp2 to promote type‐I interferon activity
Ceftazidime reduces cellular Skp2 to promote type‐I interferon activity
复制标题
DOI：
10.1111/imm.13687
复制
发表时间：
2023-08
期刊：
影响因子：
6.4
通讯作者：
Caixia Qiao;Fan Huang;Jiuyi He;Qiuyu Wu;Zhijin Zheng;Ting Zhang;Ying Miao;Yukang Yuan;Xiangjie Chen;Qian Du;Yang Xu;Depei Wu;Zhengyuan Yu;Huizhen Zheng
中科院分区：
文献类型：
--
作者：
Caixia Qiao;Fan Huang;Jiuyi He;Qiuyu Wu;Zhijin Zheng;Ting Zhang;Ying Miao;Yukang Yuan;Xiangjie Chen;Qian Du;Yang Xu;Depei Wu;Zhengyuan Yu;Huizhen Zheng
Skp2在恶性肿瘤中发挥多种作用。在这里，我们发现Skp2负调控I型干扰素（IFN‐I）介导的抗病毒活性。我们首先注意到Skp2可以促进细胞中的病毒感染。进一步的研究表明，Skp2与IFN - I受体2 （IFNAR2）相互作用，促进K48 - linked IFNAR2的多泛素化，从而加速IFNAR2蛋白的降解。Skp2介导的IFNAR2水平下调抑制IFN - I信号传导和IFN - I诱导的抗病毒活性。此外，我们首次发现抗生素ceftazidime可以作为Skp2的抑制因子。头孢他啶降低细胞Skp2水平，从而增强IFNAR2稳定性和IFN‐I抗病毒活性。本研究揭示了Skp2在调节IFN - I信号传导和IFN - I抗病毒活性中的新作用，并报道了抗生素头孢他啶是Skp2的潜在抑制因子。
Skp2 plays multiple roles in malignant tumours. Here, we revealed that Skp2 negatively regulates type‐I interferon (IFN‐I)‐mediated antiviral activity. We first noticed that Skp2 can promote virus infection in cells. Further studies demonstrated that Skp2 interacts with IFN‐I receptor 2 (IFNAR2) and promotes K48‐linked polyubiquitination of IFNAR2, which accelerates the degradation of IFNAR2 proteins. Skp2‐mediated downregulation of IFNAR2 levels inhibits IFN‐I signalling and IFN‐I‐induced antiviral activity. In addition, we uncovered for the first time that the antibiotic ceftazidime can act as a repressor of Skp2. Ceftazidime reduces cellular Skp2 levels, thus enhancing IFNAR2 stability and IFN‐I antiviral activity. This study reveals a new role of Skp2 in regulating IFN‐I signalling and IFN‐I antiviral activity and reports the antibiotic ceftazidime as a potential repressor of Skp2.