Regulation of β-Catenin Function by the IκB Kinases

Carmela Lamberti, Keng Mean Lin, Yumi Yamamoto, Udit Verma, Inder M. Verma, Steven Byers, Richard B. Gaynor

Research output: Contribution to journalArticlepeer-review

105 Scopus citations

Abstract

Both the β-catenin and the nuclear factor κB (N-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. IKKβ 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.

Original languageEnglish (US)
Pages (from-to)42276-42286
Number of pages11
JournalJournal of Biological Chemistry
Volume276
Issue number45
DOIs
StatePublished - Nov 9 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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