Syndecan-4 negatively regulates antiviral signalling by mediating RIG-I deubiquitination via CYLD.
Syndecan-4 negatively regulates antiviral signalling by mediating RIG-I deubiquitination via CYLD.
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Syndecan-4 通过 CYLD 介导 RIG-I 去泛素化来负调节抗病毒信号
DOI：
10.1038/ncomms11848
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发表时间：
2016-06-09
影响因子：
16.6
通讯作者：
Sun Q
中科院分区：
文献类型：
--
作者：
Lin W;Zhang J;Lin H;Li Z;Sun X;Xin D;Yang M;Sun L;Li L;Wang H;Chen D;Sun Q
视黄酸诱导的基因I（RIG-I）在病原体识别和抗病毒信号转换中起着重要作用发现SDC4通过反馈 - 环对照方式进行负调节RIG-I介导的抗病毒信号传导。 SDC4在机械上的作用。增强了RIG-1-钙的相互作用，并势力促进了RIG-I的K63连接去泛素化。 SDC4在CYLD介导的去泛素化依赖性过程中拮抗RIG-I的激活，从而平衡抗病毒信号，以避免对宿主细胞的有害作用。
Syndecans是在多种细胞活动中实施的跨膜蛋白聚糖。
Retinoic acid-inducible gene I (RIG-I) plays important roles in pathogen recognition and antiviral signalling transduction. Here we show that syndecan-4 (SDC4) is a RIG-I-interacting partner identified in a yeast two-hybrid screen. We find that SDC4 negatively regulates the RIG-I-mediated antiviral signalling in a feedback-loop control manner. The genetic evidence obtained by using knockout mice further emphasizes this biological role of SDC4 in antiviral signalling. Mechanistically, we show that SDC4 interacts with both RIG-I and deubiquitinase CYLD via its carboxyl-terminal intracellular region. SDC4 likely promotes redistribution of RIG-I and CYLD in a perinuclear pattern post viral infection, and thus enhances the RIG-I–CYLD interaction and potentiates the K63-linked deubiquitination of RIG-I. Collectively, our findings uncover a mechanism by which SDC4 antagonizes the activation of RIG-I in a CYLD-mediated deubiquitination-dependent process, thereby balancing antiviral signalling to avoid deleterious effects on host cells.