RKIP inhibits NF-kappaB in cancer cells by regulating upstream signaling components of the IkappaB kinase complex Article (Faculty180)

cited authors

  • Tang, Huihui; Park, Sungdae; Sun, Shao- C; Trumbly, Robert; Ren, Gang; Tsung, Eric; Yeung, Kam C


  • 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.


publication date

  • 2010

published in

start page

  • 662

end page

  • 8


  • 584