MyD88 NEDDylation negatively regulates MyD88-dependent NF-kappa B signaling through antagonizing its ubiquitination
MyD88 NEDDylation negatively regulates MyD88-dependent NF-kappa B signaling through antagonizing its ubiquitination
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MyD88 NEDDylation 通过拮抗 MyD88 的泛素化来负向调节 MyD88 依赖性 NF-kappa B 信号传导
DOI：
10.1016/j.bbrc.2016.11.084
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发表时间：
2017
影响因子：
3.1
通讯作者：
Zheng Xiaofeng
中科院分区：
文献类型：
--
作者：
Yan Fangxue;Guan Junhong;Peng Yanyan;Zheng Xiaofeng
髓样分化因子88（MyD 88）在先天免疫应答中起着核心作用，然而，其活性如何受到严格调控仍在很大程度上未知。在这项研究中，我们确定MyD 88作为一种新的底物的NEDD 8，并证明MyD 88 NEDD化拮抗其泛素化。有趣的是，响应于IL-1β的刺激，MyD 88 NEDD化下调，而其泛素化上调。我们还表明，去NEDDase NEDP 1作为这一过程的调节剂。此外，我们证明NEDD 8负性调节MyD 88的二聚化并抑制MyD 88依赖的NF-κB信号传导。综上所述，本研究表明MyD 88的NEDD化通过拮抗其遍在化来调节NF-κB活性，提示了一种调节NF-κB信号通路的新机制。
Myeloid differentiation factor 88 (MyD88) plays a central role in innate immunity response, however, how its activity is tightly regulated remains largely unknown. In this study, we identify MyD88 as a novel substrate of NEDD8, and demonstrate that MyD88 NEDDylation antagonizes its ubiquitination. Interestingly, in response to the stimulation of IL-1β, MyD88 NEDDylation is downregulated while its ubiquitination is upregulated. We also show that deNEDDylase NEDP1 serves as a regulator of this process. Furthermore, we demonstrate that NEDD8 negatively regulates the dimerization of MyD88 and suppresses MyD88-dependent NF-κB signaling. Taken together, this study reveals that NEDDylation of MyD88 regulates NF-κB activity through antagonizing its ubiquitination, suggesting a novel mechanism of modulating NF-κB signaling pathway.