PCBP2 mediates degradation of the adaptor MAVS via the HECT ubiquitin ligase AIP4

被引：283

作者：

You, Fuping ^{[1
]}

Sun, Hui ^{[1
]}

Zhou, Xiang ^{[1
]}

Sun, Wenxiang ^{[1
]}

Liang, Shimin ^{[1
]}

Zhai, Zhonghe ^{[1
]}

Jiang, Zhengfan ^{[1
]}

机构：

[1] Peking Univ, Sch Life Sci, Educ Minist, Key Lab Cell Proliferat & Differentia, Beijing 100871, Peoples R China

来源：

NATURE IMMUNOLOGY | 2009年 / 10卷 / 12期

基金：

中国国家自然科学基金;

关键词：

RIG-I; FUNCTIONAL DIVERSITY; NEDD4; FAMILY; KAPPA-B; PROTEIN; ITCH; INNATE; IDENTIFICATION; RECOGNITION; INTERACTS;

D O I：

10.1038/ni.1815

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

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页码：1300 / U10

页数：10

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