Mechanisms of Armadillo/Beta-catenin degradation

无翼(Wg)/Wnt信号通路的不适当激活经常导致人类癌症， 比如结肠癌。WG信号通过调节关键效应蛋白的细胞内水平而发生， β-连环蛋白(果蝇称为Armadillo(ARM))。大量实验证据表明，ARM是 受针对ARM降解的多蛋白复合体(破坏复合体)的负调控。 然而，关于销毁综合体如何运作的几个基本问题仍然存在。在……里面 特别是，APC蛋白在破坏复合体中的作用尚不清楚。解决……的作用 在销毁复合体中，将使用果蝇APC2作为 人类APC的模型，从这一分析中获得的信息将用于评估几个模型 销毁综合体中的APC功能。其次，E3泛素连接酶的分子组成 将定义降解ARM的物质，特别是评估ROC蛋白在ARM降解中的重要性。 最后，假设APC蛋白在转移破坏的手臂中具有第二功能 E3泛素连接酶的复合体将被研究。

Inappropriate activation of the Wingless(Wg)/Wnt signaling pathway frequently results in human cancers, such as colon cancer. Wg signaling occurs by regulating the intracellular levels of the key effector protein, beta-catenin (called Armadillo (Arm) in Drosophila). Substantial experimental evidence suggests that Arm is negatively regulated by a multi-protein complex (thedestruction complex) that targets Arm for degradation. Several fundamental questions still remain, however, concerning how the destruction complex functions. In particular, the role of the protein APC in the destruction complex remains unknown. To address the role of APC in the destruction complex, a structure/function analysis will be performed using Drosophila APC2 as a model for human APC,and the information gained from this analysis will be used to evaluate several models of APC function in the destruction complex. Secondly, the molecular composition of the E3 ubiquitin ligase that degrades Arm will be defined, specifically evaluating the importance of Roc proteins in Arm degradation. Finally, the hypothesis that APC proteins have a second function in transferring Arm from the destruction complex to E3 ubiquitin ligases will be investigated.