Regulation of β-catenin function by the IκB kinases

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