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Cell Res. 2014 Mar;24(3):359-71. doi: 10.1038/cr.2013.162. Epub 2013 Dec 10.

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

Author information

1
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
2
1] Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China [2] Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China [3] Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing 100021, China.

Abstract

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.

PMID:
24323043
PMCID:
PMC3945882
DOI:
10.1038/cr.2013.162
[Indexed for MEDLINE]
Free PMC Article
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