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Volume 24, No 3, Mar 2014

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 24 Issue 3, March 2014: 359-371

ORIGINAL ARTICLES

RACK1 modulates NF-κB activation by interfering with the interaction between TRAF2 and the IKK complex

Fan Yao1, Ling-Yun Long1, Yue-Zhen Deng1, Yuan-Yuan Feng1, Guo-Yuan Ying1, Wen-Dai Bao1, Guo Li1, Dong-Xian Guan1, Yin-Qiu Zhu1, Jing-Jing Li1 and Dong Xie1,2,3

1Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
2Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
3Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing 100021, China
Correspondence: IKK complex; inflammatory reactions; NF-κB; RACK1; sensitivity(dxie@sibs.ac.cn)

The transcription factor NF-κB plays a pivotal role in innate immunity in response to a variety of stimuli, and the coordinated regulation of this pathway determines the proper host responses to extracellular signals. In this study, we identified RACK1 as a novel negative regulator of NF-κB signaling, NF-κB-mediated cytokine induction and inflammatory reactions. RACK1 physically associates with the IKK complex in a TNF-triggered manner. This interaction interferes with the recruitment of the IKK complex to TRAF2, which is a critical step for IKK phosphorylation and subsequent activation triggered by TNF. By modulating the interaction between TRAF2 and IKK, RACK1 regulates the levels of NF-κB activation in response to different intensities of stimuli. Our findings suggest that RACK1 plays an important role in controlling the sensitivity of TNF-triggered NF-κB signaling by regulating IKK activation and provide new insight into the negative regulation of inflammatory reactions.


10.1038/cr.2013.162

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