Modulation of beta-catenin phosphorylation/degradation by cyclin-dependent kinase 2.
beta-Catenin functions as a downstream component of the Wnt/Wingless signal transduction pathway, and inappropriate control of cytosolic beta-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 beta-catenin. In ... vivo and in vitro kinase assays with cyclin-CDK2 demonstrate beta-catenin phosphorylation on residues Ser(33), Ser(37), Thr(41), and Ser(45). This phosphorylation promotes rapid degradation of cytosolic beta-catenin via the beta-TrCP-mediated proteasome pathway. Moreover, cyclin E-CDK2 contributes to rapid degradation of cytosolic beta-catenin levels during G(1) phase by regulating beta-catenin phosphorylation and subsequent degradation. In this way, CDK2 may "fine tune" beta-catenin levels over the course of the cell cycle.
Mesh Terms:
Amino Acid Motifs, Amino Acid Sequence, Animals, CDC2-CDC28 Kinases, Cell Cycle, Cell Line, Cell Line, Tumor, Cyclin-Dependent Kinase 2, Cysteine Endopeptidases, Cytoskeletal Proteins, Cytosol, Down-Regulation, G1 Phase, Glutathione Transferase, HeLa Cells, Humans, Immunoblotting, Molecular Sequence Data, Multienzyme Complexes, Phosphorylation, Plasmids, Precipitin Tests, Proteasome Endopeptidase Complex, Protein Binding, Rats, Recombinant Proteins, Serine, Signal Transduction, Subcellular Fractions, Threonine, Time Factors, Trans-Activators, Transfection, beta Catenin
Amino Acid Motifs, Amino Acid Sequence, Animals, CDC2-CDC28 Kinases, Cell Cycle, Cell Line, Cell Line, Tumor, Cyclin-Dependent Kinase 2, Cysteine Endopeptidases, Cytoskeletal Proteins, Cytosol, Down-Regulation, G1 Phase, Glutathione Transferase, HeLa Cells, Humans, Immunoblotting, Molecular Sequence Data, Multienzyme Complexes, Phosphorylation, Plasmids, Precipitin Tests, Proteasome Endopeptidase Complex, Protein Binding, Rats, Recombinant Proteins, Serine, Signal Transduction, Subcellular Fractions, Threonine, Time Factors, Trans-Activators, Transfection, beta Catenin
J. Biol. Chem.
Date: May. 07, 2004
PubMed ID: 14985333
View in: Pubmed Google Scholar
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