期刊
EMBO REPORTS
卷 13, 期 4, 页码 347-354出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/embor.2012.12
关键词
axin 2; beta-catenin; cell cycle; CDC20; Wnt signalling
资金
- Interdisciplinary Centre for Clinical Research (IZKF-Erlangen) [D12/1, J9]
Wnt/beta-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/beta-catenin target genes are low at G2/M and high at G1/S, and beta-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/beta-catenin signalling for maximal activity during G1/S.
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