1. RKIP inhibits NF-κB in cancer cells by regulating upstream signaling components of the IκB kinase complex
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Huihui Tang, Kam C. Yeung, Sungdae Park, Gang Ren, Shao Cong Sun, Eric Tsung, and Robert J. Trumbly
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Scaffold protein ,Immunoprecipitation ,Immunoblotting ,Interleukin-1beta ,Biophysics ,Gene Expression ,Phosphatidylethanolamine Binding Protein ,IκB kinase ,Biology ,Biochemistry ,Article ,NF-κB ,Cell Line ,chemistry.chemical_compound ,RKIP ,NF-KappaB Inhibitor alpha ,Structural Biology ,RNA interference ,Cell Line, Tumor ,Neoplasms ,Chlorocebus aethiops ,Genetics ,Animals ,Humans ,Phosphorylation ,Molecular Biology ,TNF Receptor-Associated Factor 6 ,Reverse Transcriptase Polymerase Chain Reaction ,Kinase ,NF-kappa B ,Ubiquitination ,Cell Biology ,MAP Kinase Kinase Kinases ,I-kappa B Kinase ,Cell biology ,Interleukin-1 Receptor-Associated Kinases ,chemistry ,COS Cells ,I-kappa B Proteins ,RNA Interference ,Negative regulatory loop ,Signal transduction ,Raf-MEK-ERK ,Protein Binding ,Signal Transduction - Abstract
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-κB pathway. Genetic and biochemical studies demonstrated that RKIP functioned as a scaffold protein facilitating the phosphorylation of IκB 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-κB transcriptional activities. Since NF-κB target gene expression is subject to negative regulation involving the optimal induction of negative regulators, our data support a hypothesis that RKIP inhibits NF-κB activity via the auto-regulatory feedback loop by rapidly inducing the expression and synthesis of inhibitors of NF-κB activation.Structured summaryMINT-7386121: TRAF6 (uniprotkb:Q9Y4K3) physically interacts (MI:0915) with RKIP (uniprotkb:P30086) by anti bait co-immunoprecipitation (MI:0006)
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