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MBC in Press, published online ahead of print April 4, 2003
Mol. Biol. Cell 10.1091/mbc.E03-01-0865

A more recent version of this article appeared on July 1, 2003
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Submitted on January 10, 2003
Revised on March 11, 2003
Accepted on March 11, 2003

{beta}-catenin regulation during the cell cycle. Implications in G2/M and apoptosis

David Olmeda1, Susanna Castel2, Senén Vilaró3, and Amparo Cano1*

1 Instituto de Investigaciones Biomédicas 'Alberto Sols', Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, 28029 Madrid, Spain
2 Servicios Científico-Técnicos, Universidad de Barcelona, Universidad de Barcelona, 08028 Barcelona, Spain
3 Departamento de Biología Celular, Universidad de Barcelona, Universidad de Barcelona, 08028 Barcelona, Spain

* Corresponding author. E-mail address: acano{at}iib.uam.es.

{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.




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