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.
Original language | English (US) |
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Pages (from-to) | 359-371 |
Number of pages | 13 |
Journal | Cell research |
Volume | 24 |
Issue number | 3 |
DOIs | |
State | Published - Mar 2014 |
Externally published | Yes |
Keywords
- IKK complex
- NF-κB
- RACK1
- inflammatory reactions
- sensitivity
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology