PCBP2 mediates degradation of the adaptor MAVS via the HECT ubiquitin ligase AIP4
PCBP2 mediates degradation of the adaptor MAVS via the HECT ubiquitin ligase AIP4
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PCBP2 通过 HECT 泛素连接酶 AIP4 介导接头 MAVS 的降解
DOI：
10.1038/ni.1815
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发表时间：
2009-12-01
影响因子：
30.5
通讯作者：
Jiang, Zhengfan
中科院分区：
文献类型：
--
作者：
You, Fuping;Sun, Hui;Jiang, Zhengfan
MAV作为Rig-I样解旋酶的唯一适配子，在先天抗病毒免疫中起着至关重要的作用。MAVS的调节对于防止过度的有害免疫反应是必不可少的。在这里，我们认为PCBP2在MAVS介导的信号转导中是一个负调控因子。PCBP2的过表达抑制了细胞对病毒感染的反应，而PCBP2的敲除则发挥了相反的作用。PCBP2在病毒感染后被诱导，并与MAVS相互作用导致MAVS蛋白酶体降解。PCBP2招募含有Hect结构域的E3连接酶AIP4来泛素化和降解MAV。MAVS在病毒感染野生型小鼠胚胎成纤维细胞后降解，但在AIP4缺陷(Ich−/−)小鼠胚胎成纤维细胞中保持稳定，并伴有极大的夸大和持续的抗病毒反应。PCBP2-AIP4轴为MAV的降解和抗病毒天然免疫的“微调”定义了一个新的信号级联。
MAVS is critical in innate antiviral immunity as the sole adaptor for RIG-I-like helicases. MAVS regulation is essential for the prevention of excessive harmful immune responses. Here we identify PCBP2 as a negative regulator in MAVS-mediated signaling. Overexpression of PCBP2 abrogated cellular responses to viral infection, whereas knockdown of PCBP2 exerted the opposite effect. PCBP2 was induced after viral infection, and its interaction with MAVS led to proteasomal degradation of MAVS. PCBP2 recruited the HECT domain–containing E3 ligase AIP4 to polyubiquitinate and degrade MAVS. MAVS was degraded after viral infection in wild-type mouse embryonic fibroblasts but remained stable in AIP4-deficient (Itch−/−) mouse embryonic fibroblasts, coupled with greatly exaggerated and prolonged antiviral responses. The PCBP2-AIP4 axis defines a new signaling cascade for MAVS degradation and 'fine tuning' of antiviral innate immunity.