泛素连接酶
先天免疫系统
泛素
细胞生物学
生物
信号转导衔接蛋白
信号转导
基因敲除
调节器
内德4
蛋白酶体
受体
基因
生物化学
作者
Zuxian Chen,Yingying Wang,Yating Song,Sumei Song,Zhuoliang He,Siyu Feng,Weiqiang Li,Yangbao Ding,Junsheng Zhang,Luxiang Zhao,Peirong Jiao
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:2023-03-15
卷期号:210 (6): 786-794
标识
DOI:10.4049/jimmunol.2200544
摘要
Abstract Mitochondrial antiviral signaling protein (MAVS) is a key adaptor in cellular innate immunity. Ubiquitination plays an important role in regulating MAVS-mediated innate immune responses; however, the molecular mechanisms underlying ubiquitination of MAVS have not been fully elucidated. In this study, we first identified the mitochondria-resident E3 ligase duck membrane-associated RING-CH 8 (duMARCH8) in ducks as a negative regulator of duck MAVS (duMAVS). Overexpression of duMARCH8 impaired the duMAVS-mediated signaling pathway, whereas knockdown of duMARCH8 resulted in the opposite effects. The suppression was due to duMARCH8 interacting with duMAVS and degrading it in a proteasome-dependent manner. We further found that duMARCH8 interacted with the 176–619 regions of duMAVS. Moreover, duMARCH8 catalyzed the K29-linked polyubiquitination of duMAVS at Lys 398 to inhibit the MAVS-mediated signaling pathway. Collectively, our findings reveal a new strategy involving MARCH8 that targets the retinoic acid–inducible gene-I–like receptor signaling pathway to regulate innate immune responses in ducks.
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