RKIP inhibits NF-κB in cancer cells by regulating upstream signaling components of the IκB kinase complex

• Published in: FEBS letters Vol. 584; no. 4; pp. 662 - 668
• Main Authors: Tang, Huihui, Park, Sungdae, Sun, Shao-Cong, Trumbly, Robert, Ren, Gang, Tsung, Eric, Yeung, Kam C.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 19.02.2010
• Subjects: Negative regulatory loop; NF-κB; Raf-MEK-ERK; RKIP; scaffold; NF-κB; Raf-MEK-ERK; Negative regulatory loop; RKIP
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2009.12.051

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. MINT-7386121: TRAF6 (uniprotkb:Q9Y4K3) physically interacts (MI:0915) with RKIP (uniprotkb:P30086) by anti bait co-immunoprecipitation (MI:0006)