Mechanisms of Armadillo/Beta-catenin degradation
犰狳/β-连环蛋白降解机制
基本信息
- 批准号:7332244
- 负责人:
- 金额:$ 5.04万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2006
- 资助国家:美国
- 起止时间:2006-01-01 至 2008-12-31
- 项目状态:已结题
- 来源:
- 关键词:APC2 geneAddressAdenomatous Polyposis ColiApoptosisBehaviorBiochemicalBiologicalBiological ModelsCancer EtiologyCancerousCell ProliferationCell physiologyCellsColon CarcinomaComplexDataDrosophila genusDrosophila inturned proteinDrosophila melanogasterFamily DasypodidaeFelis catusGenesHomologous GeneHumanIndividualMalignant NeoplasmsMediatingModelingMolecularMolecular GeneticsMutationNormal CellOncogenesPathway interactionsPropertyProteinsReagentRoleSignal PathwaySignal TransductionSignal Transduction PathwaySpeedStructureTertiary Protein StructureTumor Suppressor ProteinsUbiquitinbasebeta catenincell behaviordesignin vivonovelpreventprotein functionresearch studyubiquitin-protein ligase
项目摘要
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.
Wingless(Wg)/Wnt 信号通路的不当激活经常导致人类癌症,
例如结肠癌。 Wg 信号传导是通过调节关键效应蛋白的细胞内水平来发生的,
β-连环蛋白(在果蝇中称为犰狳(Arm))。大量实验证据表明 Arm
受到针对 Arm 降解的多蛋白复合物(破坏复合物)的负调控。
然而,关于破坏综合体如何运作的几个基本问题仍然存在。在
特别是,蛋白质 APC 在破坏复合物中的作用仍然未知。为了解决的角色
破坏复合体中的 APC,将使用果蝇 APC2 作为
人类 APC 模型,从该分析中获得的信息将用于评估多个模型
破坏复合物中 APC 功能的影响。二、E3泛素连接酶的分子组成
将定义降解 Arm 的蛋白,特别评估 Roc 蛋白在 Arm 降解中的重要性。
最后,假设 APC 蛋白具有使 Arm 免受破坏的第二个功能
将研究 E3 泛素连接酶的复合物。
项目成果
期刊论文数量(0)
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{{ truncateString('DAVID M ROBERTS', 18)}}的其他基金
Mechanisms of Armadillo/Beta-catenin degradation
犰狳/β-连环蛋白降解机制
- 批准号:
7057063 - 财政年份:2006
- 资助金额:
$ 5.04万 - 项目类别:
Mechanisms of Armadillo/Beta-catenin degradation
犰狳/β-连环蛋白降解机制
- 批准号:
7214111 - 财政年份:2006
- 资助金额:
$ 5.04万 - 项目类别:
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