MCPIP1 negatively regulate cellular antiviral innate immune responses through DUB and disruption of TRAF3-TBK1-IKKε complex.
MCPIP1 negatively regulate cellular antiviral innate immune responses through DUB and disruption of TRAF3-TBK1-IKKε complex.
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MCPIP1 通过 DUB 和破坏 TRAF3-TBK1-IKK epsilon 复合物负调节细胞抗病毒先天免疫反应
DOI：
10.1016/j.bbrc.2018.06.083
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发表时间：
2018-09-05
影响因子：
3.1
通讯作者：
Chen Z
中科院分区：
文献类型：
--
作者：
Chen X;Zhao Q;Xie Q;Xing Y;Chen Z
IFNβ天然免疫在抗病毒免疫中起重要作用。以往的研究表明，许多天然免疫途径中的重要调节蛋白可能被泛素修饰，许多去泛素化（DUB）蛋白可能影响免疫。单核细胞趋化蛋白诱导蛋白1（Monocyte chemotactic protein-inducing protein 1，MCPIP 1）是CCCH锌指蛋白之一，具有DUB功能，但其对IFNβ天然免疫的影响尚不清楚。在这项研究中，我们发现了一种新的机制，可以解释MCPIP 1如何有效地抑制IFNβ先天免疫。发现MCPIP 1负调节由RIG-I、STING、TBK 1、IRF 3激活的IFNβ表达。此外，MCPIP 1抑制IRF 3在病毒刺激下的核转位，这在I型IFN表达中起关键作用。此外，MCPIP 1与IFNβ表达途径的重要调节剂包括IPS 1、TRAF 3、TBK 1和IKKε相互作用。同时，MCPIP 1破坏了TRAF 3-TBK 1-IKKε复合物中各组分之间的相互作用。这些结果共同表明MCPIP 1是由宿主编码的先天免疫调节因子，并指出了MCPIP 1负调节IRF 3激活和I型IFNβ表达的新机制。
IFNβ innate immune plays an essential role in antiviral immune. Previous reports suggested that many important regulatory proteins in innate immune pathway may be modified by ubiquitin and that many de-ubiquitination (DUB) proteins may affect immunity. Monocyte chemotactic protein-inducing protein 1 (MCPIP1), one of the CCCH Zn finger-containing proteins, was reported to have DUB function, but its effect on IFNβ innate immune was not fully understood. In this study, we uncovered a novel mechanism that may explain how MCPIP1 efficiently inhibits IFNβ innate immune. It was found that MCPIP1 negatively regulates the IFNβ expression activated by RIG-I, STING, TBK1, IRF3. Furthermore, MCPIP1 inhibits the nuclear translocation of IRF3 upon stimulation with virus, which plays a key role in type I IFN expression. Additionally, MCPIP1 interacts with important modulators of IFNβ expression pathway including IPS1, TRAF3, TBK1 and IKKε. Meanwhile, the interaction between the components in TRAF3-TBK1-IKKε complex was disrupted by MCPIP1. These results collectively suggest MCPIP1 as an innate immune regulator encoded by the host and point to a new mechanism through which MCPIP1 negatively regulates IRF3 activation and type I IFNβ expression.
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影响因子：
20.3
作者：
Diakos, Christofer;Zhong, Sheng;Wiemels, Joseph L.
通讯作者：
Wiemels, Joseph L.
影响因子：
5.6
作者：
Kingsolver MB;Huang Z;Hardy RW
通讯作者：
Hardy RW
DOI：
10.4049/jimmunol.1601551
发表时间：
2017-01-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Monin L;Gudjonsson JE;Childs EE;Amatya N;Xing X;Verma AH;Coleman BM;Garg AV;Killeen M;Mathers A;Ward NL;Gaffen SL
通讯作者：
Gaffen SL
影响因子：
12.4
作者：
Cohen P;Strickson S
通讯作者：
Strickson S
SARS冠状病毒木瓜蛋白酶样蛋白酶通过与STING-TRAF3-TBK1复合物相互作用抑制I型干扰素信号通路
影响因子：
21.1
作者：
Chen, Xiaojuan;Yang, Xingxing;Zheng, Yang;Yang, Yudong;Xing, Yaling;Chen, Zhongbin
通讯作者：
Chen, Zhongbin