E3 ubiquitin ligase MID1 ubiquitinates and degrades type-I interferon receptor 2.

Abstract

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.

• Authors: Xiangjie Chen, Qian Zhao, Ying Xu, Qiuyu Wu, Renxia Zhang, Qian Du, 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
• Journal: Immunology (Immunology) Vol. 167 Issue 3 Pg. 398-412 (11 2022) ISSN: 1365-2567 [Electronic] England
• PMID: 35794827 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 John Wiley & Sons Ltd.

Chemical References

• Antiviral Agents
• Interferon Type I
• Ubiquitin-Protein Ligases

Topics

• Antiviral Agents (pharmacology)
• Interferon Type I (metabolism)
• Proteolysis
• Ubiquitin-Protein Ligases (genetics, metabolism)
• Ubiquitination