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

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 signalin...

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Bibliographic Details
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
LanguageEnglish
Published 2014
Subjects
IKK
NF-kB
NF-κB
TNF-α
互干扰
复合物
活化
相互作用
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Summary: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.
Bibliography: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.
31-1568/Q
IKK complex; inflammatory reactions; NF-KB; RACK1; sensitivity
ISSN:1001-0602
1748-7838