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

被引：81
作者：
Hadjihannas, Michel V. [1 ]
Bernkopf, Dominic B. [1 ]
Brueckner, Martina [1 ]
Behrens, Juergen [1 ]
机构：
[1] Univ Erlangen Nurnberg, Nikolaus Fiebiger Ctr Mol Med, D-91054 Erlangen, Germany
来源：
EMBO REPORTS | 2012年 / 13卷 / 04期
关键词：
axin; 2; beta-catenin; cell cycle; CDC20; Wnt signalling; PHOSPHORYLATED BETA-CATENIN; CHROMOSOMAL INSTABILITY; FUNCTIONAL INTERACTION; UP-REGULATION; WNT; CANCER; GROWTH; TRANSCRIPTION; INHIBITION; ACTIVATION;
D O I：
10.1038/embor.2012.12
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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.
引用
收藏
页码：347 / 354
页数：8
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