RKIP inhibits NF-kappaB in cancer cells by regulating upstream signaling components of the IkappaB kinase complex.

RKIP was first identified as an inhibitor of the Raf-MEK-ERK signaling pathway. RKIP was also found to play an important role in the NF-kappaB pathway. Genetic and biochemical studies demonstrated that RKIP functioned as a scaffold protein facilitating the phosphorylation of IkappaB by upstream kinases. However, contrary to what one ...
would expect of a scaffold protein, our results show that RKIP has an overall inhibitory effect on the NF-kappaB transcriptional activities. Since NF-kappaB target gene expression is subject to negative regulation involving the optimal induction of negative regulators, our data support a hypothesis that RKIP inhibits NF-kappaB activity via the auto-regulatory feedback loop by rapidly inducing the expression and synthesis of inhibitors of NF-kappaB activation.
Mesh Terms:
Animals, COS Cells, Cell Line, Cell Line, Tumor, Cercopithecus aethiops, Gene Expression, Humans, I-kappa B Kinase, I-kappa B Proteins, Immunoblotting, Immunoprecipitation, Interleukin-1 Receptor-Associated Kinases, Interleukin-1beta, MAP Kinase Kinase Kinases, NF-kappa B, Neoplasms, Phosphatidylethanolamine Binding Protein, Phosphorylation, Protein Binding, RNA Interference, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, TNF Receptor-Associated Factor 6, Ubiquitination
FEBS Lett.
Date: Feb. 19, 2010
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