Journal
CELL RESEARCH
Volume 24, Issue 3, Pages 359-371Publisher
INST BIOCHEMISTRY & CELL BIOLOGY
DOI: 10.1038/cr.2013.162
Keywords
IKK complex; inflammatory reactions; NF-kappa B; RACK1; sensitivity
Categories
Funding
- National Basic Research Program of China [2010CB912102]
- Ministry of Science and Technology Key Program [2012ZX10002009-017]
- National Natural Science Foundation of China [81230058, 30930023, 31100551, 31201046, 81021002]
- CAS/SAFEA International Partnership Program for Creative Research Teams
- Shanghai Institutes for Biological Sciences
- Chinese Academy of Sciences [SIBS2012004]
- Technology Commission of Shanghai Municipality [12XD1405600]
Ask authors/readers for more resources
The transcription factor NF-kappa B 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-kappa B signaling, NF-.B-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-kappa B 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-kappa B signaling by regulating IKK activation and provide new insight into the negative regulation of inflammatory reactions.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available