Regulation of beta-catenin function by the IkappaB kinases.
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.
Lamberti
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C
Division of Hematology-Oncology, Department of Medicine, Harold Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Lin
K M
KM
Yamamoto
Y
Y
Verma
U
U
Verma
I M
IM
Byers
S
S
Gaynor
R B
RB
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
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