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

• Published in: 细胞研究：英文版 no. 3; pp. 359 - 371
• Main Author: Fan Yao Ling-Yun Long Yue-Zhen Deng Yuan-Yuan Feng Guo-Yuan Ying Wen-Dai Bao Guo Li Dong-Xian Guan Yin-Qiu Zhu Jing-Jing Li Dong Xie
• Format: Journal Article
• Language: English
• Published: 2014
• Subjects: IKK; NF-kB; NF-κB; TNF-α; 互干扰; 复合物; 活化; 相互作用
• ISSN: 1001-0602

The transcription factor NF-kB 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-KB signaling, NF-KB-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-kB activation in response to different intensities of stimuli. Our findings suggest that RACKI plays an important role in controlling the sensitivity of TNF-triggered NF-KB signaling by regulating IKK activation and provide new insight into the negative regulation of inflammatory reactions.