Regulation of β-Catenin Function by the IκB Kinases

Both the β-catenin and the nuclear factor κB (NF-κB) proteins are important regulators of gene expression and cellular proliferation. Two kinases, IKKα and IKKβ, are critical activators of the NF-κB pathway. Here we present evidence that these kinases are also important in the regulation of β-catenin function. IKKα- and IKKβ-deficient mouse embryo fibroblasts exhibited different patterns of β-catenin cellular localization. IKKβ decreases β-catenin-dependent transcriptional activation, while IKKα increases β-catenin-dependent transcriptional activity. IKKα and IKKβ interact with and phosphorylate β-catenin using both in vitro and in vivo assays. Our results suggest that differential interactions of β-catenin with IKKα and IKKβ may in part be responsible for regulating β-catenin protein levels and cellular localization and integrating signaling events between the NF-κB and Wingless pathways.