Control of β-catenin stability:: Reconstitution of the cytoplasmic steps of the wnt pathway in Xenopus egg extracts

被引：299

作者：

Salic, A ^{[1
]}

Lee, E ^{[1
]}

Mayer, L ^{[1
]}

Kirschner, MW ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA

来源：

MOLECULAR CELL | 2000年 / 5卷 / 03期

关键词：

D O I：

10.1016/S1097-2765(00)80446-3

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：

Regulation of beta-catenin degradation by intracellular components of the wnt pathway was reconstituted in cytoplasmic extracts of Xenopus eggs and embryos. The ubiquitin-dependent beta-catenin degradation in extracts displays a biochemical requirement for axin, GSK3, and APC. Axin dramatically accelerates while dishevelled inhibits beta-catenin turnover. Through another domain, dishevelled recruits GBP/Frat1 to the APC-axin-GSK3 complex. Our results confirm and extend models in which inhibition of GSK3 has two synergistic effects: (1) reduction of APC phosphorylation and loss of affinity for beta-catenin and (2) reduction of beta-catenin phosphorylation and consequent loss of its affinity for the SCF ubiquitin ligase complex. Dishevelled thus stabilizes beta-catenin, which can dissociate from the APC/axin complex and participate in transcriptional activation.

引用

页码：523 / 532

页数：10

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