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 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.
Olmeda
David
D
Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, 28029 Madrid, Spain.
Castel
Susanna
S
Vilaró
Senén
S
Cano
Amparo
A
D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D018385:Centrosome / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004285:Dogs; D005434:Flow Cytometry; D016195:G2 Phase / Q000502:physiology*; D006801:Humans; D051379:Mice; D018613:Microscopy, Confocal; D008938:Mitosis / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism*; D051176:beta Catenin
D025601:Adenomatous Polyposis Coli Protein; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin