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Vol. 14, Issue 7, 2844-2860, July 2003
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-Catenin Regulation during the Cell Cycle: Implications in G2/M and Apoptosis

*Instituto de Investigaciones Biomédicas
"Alberto Sols," Consejo Superior de Investigaciones
Científicas-Universidad Autónoma de Madrid, 28029 Madrid, Spain;
Servicios Científico-Técnicos,
Universidad de Barcelona; and
Departamento de
Biología Celular, Universidad de Barcelona, 08028 Barcelona,
Spain
Submitted January 10, 2003;
Revised March 11, 2003;
Accepted March 11, 2003
Monitoring Editor: Richard Hynes
-catenin is a multifunctional protein involved in cell-cell adhesion
and Wnt signal transduction.
-Catenin signaling has been proposed to act
as inducer of cell proliferation in different tumors. However, in some
developmental contexts and cell systems
-catenin also acts as a positive
modulator of apoptosis. To get additional insights into the role of
-Catenin in the regulation of the cell cycle and apoptosis, we have
analyzed the levels and subcellular localization of endogenous
-catenin
and its relation with adenomatous polyposis coli (APC) during the cell cycle
in S-phasesynchronized epithelial cells.
-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
-catenin and APC is observed
during S and G2 phases. In addition, strong colocalization of APC with
centrosomes, but not
-catenin, is detected in M phase. Interestingly,
overexpression of a stable form of
-catenin, or inhibition of endogenous
-catenin degradation, in epidermal keratinocyte cells induces a G2 cell
cycle arrest and leads to apoptosis. These results support a role for
-catenin in the control of cell cycle and apoptosis at G2/M in normal
and transformed epidermal keratinocytes.
Abbreviations used: APC, adenomatous polyposis coli; GSK-3
, glycogen
synthase kinase 3
; MDCK, Madin-Darby canine kidney; MEF, murine
embryonic fibroblasts; MTOC, microtubule organizing center; Siah-1, seven in
absentia-1 homologous protein.
Online version of this article contains video materials for some figures.
Online version is available at
www.molbiolcell.org.
Corresponding author. E-mail address:
acano{at}iib.uam.es.
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