RNF4 negatively regulates NF‐κB signaling by down‐regulating TAB2. Issue 19 (20th August 2015)

• Record Type: Journal Article
• Authors: Tan, Bo; Mu, Rui; Chang, Yan; Wang, Yu-Bo; Wu, Min; Tu, Hai-Qing; Zhang, Yu-Cheng; Guo, Sai-Sai; Qin, Xuan-He; Li, Tao; Li, Wei-Hua; Zhang, Xue-Min; Li, Ai-Ling; Li, Hui-Yan
• Is Part Of: FEBS letters. Volume 589:Issue 19(2015) Part B
• Page Start: 2850
• Page End: 2858
• Publication Date: 2015-08-20
• Subjects: NF-κB -- nuclear factor kappa B -- TNFα -- tumor necrosis factor alpha -- IL-1β -- interleukin 1 beta -- NF-κB -- TNFα -- IL-1β -- RNF4 -- TAB2; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2015.07.051
• Languages: English
• ISSNs: 0014-5793

Abstract

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. Abstract : We designed a siRNA library targeted genes correlated with ubiquitin‐binding. We screened canonical NF‐κB signaling for regulators by using the library. One of the candidates RNF4 was confirmed as a negative regulator of NF‐κB signaling. RNF4 interacted with and down‐regulated TAB2 through lysosomal pathway.