SENP6 restricts the IFN-I-induced signaling pathway and antiviral activity by deSUMOylating USP8.

Autor: Guo J; Jiangsu Provincial Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, 215123, China., Zheng H; Jiangsu Provincial Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, 215123, China. huizheng@suda.edu.cn., Xiong S; Jiangsu Provincial Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, 215123, China. sdxiong@suda.edu.cn.
Jazyk: angličtina
Zdroj: Cellular & molecular immunology [Cell Mol Immunol] 2024 Aug; Vol. 21 (8), pp. 892-904. Date of Electronic Publication: 2024 Jun 21.
DOI: 10.1038/s41423-024-01193-3
Abstrakt: Type I interferon (IFN-I) exhibits broad-spectrum antiviral properties and is commonly employed in clinical for the treatment of viral infections. In this study, we unveil SENP6 as a potent regulator of IFN-I antiviral activity. SENP6 does not impact the production of IFN-I induced by viruses but rather modulates IFN-I-activated signaling. Mechanistically, SENP6 constitutively interacts with USP8 and inhibits the SUMOylation of USP8, consequently restricting the interaction between USP8 and IFNAR2. The dissociation of USP8 from IFNAR2 enhances IFNAR2 ubiquitination and degradation, thus attenuating IFN-I antiviral activity. Correspondingly, the downregulation of SENP6 promotes the interaction between USP8 and IFNAR2, leading to a reduction in IFNAR2 ubiquitination and, consequently, an enhancement in IFN-I-induced signaling. This study deciphers a critical deSUMOylation-deubiquitination crosstalk that finely regulates the IFN-I response to viral infection.
(© 2024. The Author(s), under exclusive licence to CSI and USTC.)
Databáze: MEDLINE
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