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EMBO Rep. 2012 Apr;13(4):347-54. doi: 10.1038/embor.2012.12.

Cell cycle control of Wnt/β-catenin signalling by conductin/axin2 through CDC20.

Author information

1
Nikolaus-Fiebiger-Center of Molecular Medicine, University of Erlangen, Glueckstrasse 6, 91054 Erlangen, Germany.

Abstract

Wnt/β-catenin signalling regulates cell proliferation by modulating the cell cycle and is negatively regulated by conductin/axin2/axil. We show that conductin levels peak at G2/M followed by a rapid decline during return to G1. In line with this, Wnt/β-catenin target genes are low at G2/M and high at G1/S, and β-catenin phosphorylation oscillates during the cell cycle in a conductin-dependent manner. Conductin is degraded by the anaphase-promoting complex/cyclosome cofactor CDC20. Knockdown of CDC20 blocks Wnt signalling through conductin. CDC20-resistant conductin inhibits Wnt signalling and attenuates colony formation of colorectal cancer cells. We propose that CDC20-mediated degradation of conductin regulates Wnt/β-catenin signalling for maximal activity during G1/S.

PMID:
22322943
PMCID:
PMC3321148
DOI:
10.1038/embor.2012.12
[Indexed for MEDLINE]
Free PMC Article

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