title: RNF4 negatively regulates NF-κB signaling by down-regulating TAB2.
abstract: Most of NF-κB (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-κB pathway, including RNF4. Overexpression of RNF4 impaired NF-κB activation in a dose-dependent manner, whereas RNF4 knockdown potentiated NF-κB 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-κB signaling.
authors: Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing 100850, China.
authors: Bo
authors: B
authors: Tan
authors: Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing 100850, China.
authors: Rui
authors: R
authors: Mu
authors: Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing 100850, China.
authors: Yan
authors: Y
authors: Chang
authors: Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing 100850, China.
authors: Yu-Bo
authors: YB
authors: Wang
authors: Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing 100850, China.
authors: Min
authors: M
authors: Wu
authors: Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing 100850, China.
authors: Hai-Qing
authors: HQ
authors: Tu
authors: Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing 100850, China.
authors: Yu-Cheng
authors: YC
authors: Zhang
authors: Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing 100850, China.
authors: Sai-Sai
authors: SS
authors: Guo
authors: Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing 100850, China.
authors: Xuan-He
authors: XH
authors: Qin
authors: Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing 100850, China.
authors: Tao
authors: T
authors: Li
authors: Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing 100850, China.
authors: Wei-Hua
authors: WH
authors: Li
authors: Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing 100850, China.
authors: Xue-Min
authors: XM
authors: Zhang
authors: Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing 100850, China.
authors: Ai-Ling
authors: AL
authors: Li
authors: Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing 100850, China. Electronic address: hyli@ncba.ac.cn.
authors: Hui-Yan
authors: HY
authors: Li
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D059748:Proteolysis / Q000187:drug effects; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D053583:Interleukin-1beta; D020930:MAP Kinase Kinase Kinases; D016328:NF-kappa B; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D014157:Transcription Factors; D025801:Ubiquitin; D000099151:MAP Kinase Kinase Kinase 7; C114070:RNF4 protein, human; C498761:Tab2 protein, mouse
keywords: IL-1β; NF-κB; RNF4; TAB2; TNFα