E3 ubiquitin ligase MID1 ubiquitinates and degrades type-I interferon receptor 2
E3 ubiquitin ligase MID1 ubiquitinates and degrades type-I interferon receptor 2
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DOI：
10.1111/imm.13544
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Yukang Yuan
中科院分区：
文献类型：
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作者：
Xiangjie Chen;Qian Zhao;Ying Xu;Qiuyu Wu;Renxia Zhang;Qian Du;Ying Miao;Ying Miao;Yibo Zuo;Hong-Guang Zhang;Fan Huang;Tengfei Ren;Jiuyi He;Caixia Qiao;Yue Li;Shifeng Li;Yang Xu;Depei Wu;Zhengyuan Yu;Haitao Lv;Jun Wang;Hui Zheng;Yukang Yuan
Type I interferon (IFN-I) is a common biological molecule used for the treatment of viral diseases. However, the clinical antiviral efficacy of IFN-I needs to be greatly improved. In this study, IFN-I receptor 2 (IFNAR2) was revealed to undergo degradation at the protein level in cells treated with IFN-I for long periods of time. Further studies found a physical interaction between the E3 ubiquitin ligase midline-1 (MID1) and IFNAR2. As a consequence, MID1 induced both K48- and K63-linked polyubiquitination of IFNAR2, which promoted IFNAR2 protein degradation in a lysosome-dependent manner. Conversely, knockdown of MID1 largely restricted IFN-I-induced degradation of IFNAR2. Importantly, MID1 regulated the strength of IFN-I signalling and IFN-I-induced antiviral activity. These findings reveal a regulatory mechanism of IFNAR2 ubiquitination and protein stability in IFN-I signalling, which could provide a potential target for improving the antiviral efficacy of IFN-I.
