Modulation of β-Catenin Phosphorylation/Degradation by Cyclin-dependent Kinase 2

Chun Shik Park, Sung Il Kim, Mi Su Lee, Cho Ya Youn, Dae Joong Kim, Eek Hoon Jho, Woo Keun Song

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

β-Catenin functions as a downstream component of the Wnt/Wingless signal transduction pathway, and inappropriate control of cytosolic β-catenin is a crucial step in the genesis of several human cancers. Here we demonstrate that cyclin-dependent kinase 2 (CDK2) in association with cyclin A or cyclin E directly binds to β-catenin. In vivo and in vitro kinase assays with cyclin-CDK2 demonstrate β-catenin phosphorylation on residues Ser33, Ser37, Thr41, and Ser45. This phosphorylation promotes rapid degradation of cytosolic β-catenin via the β-TrCP-mediated proteasome pathway. Moreover, cyclin E-CDK2 contributes to rapid degradation of cytosolic β-catenin levels during G1 phase by regulating β-catenin phosphorylation and subsequent degradation. In this way, CDK2 may "fine tune" β-catenin levels over the course of the cell cycle.

Original languageEnglish
Pages (from-to)19592-19599
Number of pages8
JournalJournal of Biological Chemistry
Volume279
Issue number19
DOIs
StatePublished - 7 May 2004

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