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

页码：347 / 354

页数：8

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