RNF4 negatively regulates NF-κB signaling by down-regulating TAB2

被引:26
作者
Tan, Bo [1 ]
Mu, Rui [1 ]
Chang, Yan [1 ]
Wang, Yu-Bo [1 ]
Wu, Min [1 ]
Tu, Hai-Qing [1 ]
Zhang, Yu-Cheng [1 ]
Guo, Sai-Sai [1 ]
Qin, Xuan-He [1 ]
Li, Tao [1 ]
Li, Wei-Hua [1 ]
Zhang, Xue-Min [1 ]
Li, Ai-Ling [1 ]
Li, Hui-Yan [1 ]
机构
[1] Natl Ctr Biomed Anal, Inst Basic Med Sci, Beijing 100850, Peoples R China
基金
中国国家自然科学基金;
关键词
NF-kappa B; TNF alpha; IL-1; beta; RNF4; TAB2; UBIQUITIN E3 LIGASE; ACTIVATION; ALPHA; PML;
D O I
10.1016/j.febslet.2015.07.051
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Most of NF-kappa B (nuclear factor kappa B) signaling molecules have various types of post-translational modifications. In this study, we focused on ubiquitination and designed a siRNA library including most ubiquitin-binding domains. With this library, we identified several candidate regulators of canonical NF-kappa B pathway, including RNF4. Overexpression of RNF4 impaired NF-kappa B activation in a dose-dependent manner, whereas RNF4 knockdown potentiated NF-kappa B activation. We showed that RNF4 interacts with the TAK1-TAB2-TAB3 complex, but not TAB1. Further, we found that RNF4 specifically down-regulated TAB2 through a lysosomal pathway, and knockdown of RNF4 impaired endogenous TAB2 degradation. Therefore, our findings will provide new insights into the negative regulation of NF-kappa B signaling. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:2850 / 2858
页数:9
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