Beta-catenin regulation during the cell cycle: implications in G2/M and apoptosis

Beta-catenin is a multifunctional protein involved in cell-cell adhesion and Wnt signal transduction. Beta-catenin signaling has been proposed to act as inducer of cell proliferation in different tumors. However, in some developmental contexts and cell systems beta-catenin also acts as a positive mo...

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Bibliographic Details
Published in:Molecular biology of the cell 2003-07, Vol.14 (7), p.2844-2860
Main Authors: Olmeda, David, Castel, Susanna, Vilaró, Senén, Cano, Amparo
Format: Article
Language:English
Subjects:
Adenomatous Polyposis Coli Protein - metabolism
Animals
Apoptosis - physiology
beta Catenin
Cell Adhesion - physiology
Cell Nucleus - metabolism
Cells, Cultured
Centrosome - metabolism
Cytoskeletal Proteins - metabolism
Dogs
Flow Cytometry
G2 Phase - physiology
Humans
Mice
Microscopy, Confocal
Mitosis - physiology
Trans-Activators - metabolism
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Summary:Beta-catenin is a multifunctional protein involved in cell-cell adhesion and Wnt signal transduction. Beta-catenin signaling has been proposed to act as inducer of cell proliferation in different tumors. However, in some developmental contexts and cell systems beta-catenin also acts as a positive modulator of apoptosis. To get additional insights into the role of beta-catenin in the regulation of the cell cycle and apoptosis, we have analyzed the levels and subcellular localization of endogenous beta-catenin and its relation with adenomatous polyposis coli (APC) during the cell cycle in S-phase-synchronized epithelial cells. Beta-catenin levels increase in S phase, reaching maximum accumulation at late G2/M and then abruptly decreasing as the cells enter into a new G1 phase. In parallel, an increased cytoplasmic and nuclear localization of beta-catenin and APC is observed during S and G2 phases. In addition, strong colocalization of APC with centrosomes, but not beta-catenin, is detected in M phase. Interestingly, overexpression of a stable form of beta-catenin, or inhibition of endogenous beta-catenin degradation, in epidermal keratinocyte cells induces a G2 cell cycle arrest and leads to apoptosis. These results support a role for beta-catenin in the control of cell cycle and apoptosis at G2/M in normal and transformed epidermal keratinocytes.
ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.E03-01-0865