Control of β-catenin stability:: Reconstitution of the cytoplasmic steps of the wnt pathway in Xenopus egg extracts
Control of β-catenin stability:: Reconstitution of the cytoplasmic steps of the wnt pathway in Xenopus egg extracts
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DOI：
10.1016/s1097-2765(00)80446-3
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发表时间：
2000-03-01
期刊：
影响因子：
16
通讯作者：
Kirschner, MW
中科院分区：
文献类型：
--
作者：
Salic, A;Lee, E;Kirschner, MW
在爪蟾卵和胚胎的细胞质提取物中重建了wnt通路胞内组分对β -连环蛋白降解的调节。提取物中泛素依赖性β -连环蛋白的降解显示出对轴蛋白、GSK3和APC的生化要求。轴蛋白急剧加速，而凌乱抑制-连环蛋白的周转。通过另一个结构域，disheveld将GBP/Frat1招募到APC-axin-GSK3复合体。我们的研究结果证实并扩展了抑制GSK3具有两种协同效应的模型：(1)降低APC磷酸化并失去对β -连环蛋白的亲和力；(2)降低β -连环蛋白磷酸化并因此失去对SCF泛素连接酶复合物的亲和力。因此，凌乱可以稳定β -连环蛋白，β -连环蛋白可以从APC/轴蛋白复合物中分离并参与转录激活。
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.