title: Regulation of beta-catenin function by the IkappaB kinases.
abstract: Both the beta-catenin and the nuclear factor kappaB (NF-kappaB) proteins are important regulators of gene expression and cellular proliferation. Two kinases, IKKalpha and IKKbeta, 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. IKKalpha- and IKKbeta-deficient mouse embryo fibroblasts exhibited different patterns of beta-catenin cellular localization. IKKbeta decreases beta-catenin-dependent transcriptional activation, while IKKalpha increases beta-catenin-dependent transcriptional activity. IKKalpha and IKKbeta interact with and phosphorylate beta-catenin using both in vitro and in vivo assays. Our results suggest that differential interactions of beta-catenin with IKKalpha and IKKbeta 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.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Harold Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: C
authors.initials: C
authors.lastname: Lamberti
authors.forename: K M
authors.initials: KM
authors.lastname: Lin
authors.forename: Y
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: U
authors.initials: U
authors.lastname: Verma
authors.forename: I M
authors.initials: IM
authors.lastname: Verma
authors.forename: S
authors.initials: S
authors.lastname: Byers
authors.forename: R B
authors.initials: RB
authors.lastname: Gaynor
mesh_terms: D000818:Animals; D019556:COS Cells; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000502:physiology*; D051550:I-kappa B Kinase; D051379:Mice; D016328:NF-kappa B / Q000502:physiology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D015534:Trans-Activators; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D051176:beta Catenin
chemical_list: C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D016328:NF-kappa B; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; D051176:beta Catenin; D017346:Protein Serine-Threonine Kinases; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase; C496562:Ikbkb protein, mouse; C496566:Ikbke protein, mouse