β-Catenin regulation during the cell cycle: Implications in G2/M and apoptosis

Copyright © by American Society for Cell Biology.-- Final full-text version of the paper available at: http://www.molbiolcell.org/content/vol14/issue7/ .-- Supplementary material available at: http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=165681&blobname=mbc_14_7_2844__.html
β-catenin is a multifunctional protein involved in cell-cell adhesion and Wnt signal transduction. β-Catenin signaling has been proposed to act as inducer of cell proliferation in different tumors. However, in some developmental contexts and cell systems β-catenin also acts as a positive modulator of apoptosis. To get additional insights into the role of β-Catenin in the regulation of the cell cycle and apoptosis, we have analyzed the levels and subcellular localization of endogenous β-catenin and its relation with adenomatous polyposis coli (APC) during the cell cycle in S-phase–synchronized epithelial cells. β-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 β-catenin and APC is observed during S and G2 phases. In addition, strong colocalization of APC with centrosomes, but not β-catenin, is detected in M phase. Interestingly, overexpression of a stable form of β-catenin, or inhibition of endogenous β-catenin degradation, in epidermal keratinocyte cells induces a G2 cell cycle arrest and leads to apoptosis. These results support a role for β-catenin in the control of cell cycle and apoptosis at G2/M in normal and transformed epidermal keratinocytes.
This work was supported by grants from the Comisión Interministerial de Ciencia y Tecnología (SAF98–0085-C03–01 and SAF2001–2819), Instituto de Salud Carlos III (FIS01/1174) and Comunidad Autónoma de Madrid (08.1/0055/2000) to AC. During the realization of this work D.O. was a predoctoral fellow of the Spanish Ministry of Science and Technology.