Cellular Functions of the Tumor Suppressor APC

肿瘤抑制因子 APC 的细胞功能

• 批准号: 7596849
• 负责人: BROOKE M MCCARTNEY
• 金额: $ 25.05万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-15 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7596849
• 关键词: APC2 gene; Actins; Adenomatous Polyposis Coli; Adenomatous Polyposis Coli Protein; Affect; Attention; Behavior; Binding; Biochemical; Biochemical Genetics; Biological Assay; COX7A2L Protein; Cadherins; Cell Cycle; Cell physiology; Centrosome; Colon Carcinoma; Complex; Cultured Cells; Cytoskeletal Modeling; Cytoskeleton; DNA Sequence Rearrangement; Data; Development; Drosophila genus; Embryo; Family; Family Dasypodidae; Filament; Functional disorder; Goals; Homologous Gene; Imaging Techniques; Inherited; Life; Malignant Neoplasms; Microfilaments; Microtubule Stabilization; Microtubules; Modeling; Mus; Mutation; Normal Cell; Pathway interactions; Phosphorylation; Phosphotransferases; Play; Plus End of the Microtubule; Process; Protein Dynamics; Proteins; Regulation; Research Personnel; Role; Signal Transduction; Signal Transduction Pathway; Structure; System; Tertiary Protein Structure; Testing; Tumor Suppressor Proteins; fly; genetic regulatory protein; in vitro Assay; in vivo; rho

DESCRIPTION (provided by applicant): The colon cancer tumor suppressor Adenomatous polyposis coli (APC) acts as an essential negative regulator of the Wnt signal transduction pathway and also has fundamental roles in the regulation of the actin and microtubule cytoskeletons. The precise mechanisms by which APC proteins influence the cytoskeleton have not been defined and may contribute to the development of colon cancer. We have developed an in vivo system in which to study the cytoskeletal functions of Drosophila APC2 using the Drosophila syncytial embryo as a model for cytoskeletal organization. Here, dynamic rearrangements of cortical actin during the cell cycle are orchestrated by a number of known actin regulatory proteins and by interactions with centrosomes and microtubules. We have previously shown that Drosophila APC2 plays a role in organization of the syncytial cytoskeleton in a complex including the Drosophila B-catenin homolog, Armadillo, and a-catenin. Our continued study of APC2 in this system revealed that APC2 functions to organize actin structures in the syncytial embryo and that this function is carried out in part with a Drosophila formin homology domain protein Diaphanous. The overall goals of this project include defining the molecular interactions of APC2 within the Armadillo-a-catenin complex and the Diaphanous complex and to understand in detail how these complexes are functioning to organize the actin cytoskeleton using biochemical assays, live imaging techniques, analysis of actin and microtubule organization and behavior, and identification of other proteins partners and regulators. These findings will contribute not only to our appreciation of normal cell processes, but also to our understanding of cellular dysfunction and cancer.

描述（由申请人提供）：结肠癌肿瘤抑制腺瘤性息肉病（APC）是Wnt信号转导途径的基本负调节剂，并且在肌动蛋白和微管细胞骨骼的调节中也具有基本作用。 APC蛋白会影响细胞骨架的确切机制尚未定义，并可能有助于结肠癌的发展。我们已经开发了一个体内系统，该系统在其中使用果蝇合胞胞菌作为细胞骨架组织的模型来研究果蝇APC2的细胞骨架功能。在这里，细胞周期中皮质肌动蛋白的动态重排由许多已知的肌动蛋白调节蛋白以及与中心体和微管的相互作用来策划。我们先前已经表明，果蝇APC2在包括果蝇B-catenin同源物，Armadillo和A-catenin在内的复合物中的合成细胞骨架组织中起作用。我们在该系统中对APC2的持续研究表明，APC2在合成胚胎中组织肌动蛋白结构的功能，并且该功能部分用果蝇formin同源性结构蛋白透射蛋白进行。该项目的总体目标包括定义AMADILLO-A-A-CATENIN复合物和驱动式复合物中APC2的分子相互作用，并详细了解这些复合物如何使用生物化学测定法，使用生物化学测定法，实时成像技术，肌动蛋白和微蛋白组织和微管组织和行为和其他Protifitions和其他Protifitions和其他蛋白质的构成和其他蛋白质的组合和praffitions和其他protifitions和其他蛋白质的彼此来组织肌动蛋白细胞骨架。这些发现不仅会促进我们对正常细胞过程的欣赏，还将有助于我们对细胞功能障碍和癌症的理解。