SCF complex and the Drosophila centrosome cycle

SCF 复合体和果蝇中心体循环

• 批准号: 7666730
• 负责人: Edward John Wojcik
• 金额: $ 25.6万
• 依托单位: LSU HEALTH SCIENCES CENTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7666730
• 关键词: Address; Affect; Aneuploidy; Appearance; Behavior; Biochemical; Biology; Cell Cycle; Cell Death; Cell division; Cells; Centrosome; Centrosome Pathway; Complex; Cyclin E; Data; Defect; Drosophila genus; Eukaryota; Event; F Box Domain; Family; Genetic; Genetic Screening; Genomic Instability; Glycogen Synthase Kinase 3; Goals; Human; Interphase; Investigation; Knowledge; Limb structure; Malignant Neoplasms; Mitosis; Mitotic; Mitotic Spindle Apparatus; Molecular; Morphogenesis; Mutation; Organelles; Pathway interactions; Phase; Play; Polyploid Cells; Prevention; Proteins; Regulation; Research; Research Personnel; Role; Screening procedure; System; Ubiquitination; cancer cell; cancer therapy; design; genetic analysis; multicatalytic endopeptidase complex; neuroblast; novel diagnostics; programs; research study; therapeutic target; ubiquitin-protein ligase

DESCRIPTION (provided by applicant): Centrosomes play an important role in the morphogenesis and function of the mitotic apparatus. Defects in the regulation of this organelle, such as over-replication, result in increased genetic instability and are associated with numerous types of human cancer cells. The line of investigation presented in this proposal will result in the characterization of regulatory components of centrosome function, establish a mechanism for the regulation of the termination of centrosome replication and discover new centrosome-associated proteins. The experimental system utilized in these experiments is well suited for the genetic, cytological, and molecular approaches that we propose. Our studies of Slimb in Drosophila are designed to analyze cell cycle functions for this subunit of the SCF complex, and to characterize putative Slimb-interacting centrosome pathway components. Our genetic analyses will reveal additional components of the slimb pathway and begin to elucidate their functions. Because this strategy can potentially identify other components of the slimb pathway besides proteins that come into direct contact with Slimb, our approach compliments existing efforts at biochemical purification of SCF components. Finally, as inroads are made toward a mechanism by which Slimb affects centrosome function, an unbiased genetic screen for additional centrosome-associated proteins will provide additional puzzle pieces in our understanding of the function of centrosomes in cell division. These discoveries will provide new diagnostic or therapeutic targets for the prevention or treatment of cancer.

描述（由申请方提供）：中心体在有丝分裂器的形态发生和功能中发挥重要作用。这种细胞器的调节缺陷，如过度复制，导致遗传不稳定性增加，并与许多类型的人类癌细胞有关。在这项建议中提出的调查线将导致在中心体功能的监管组件的特性，建立一个机制，为中心体复制的终止和发现新的中心体相关蛋白的监管。这些实验中使用的实验系统非常适合我们提出的遗传学、细胞学和分子方法。我们的研究Slimb在果蝇中的SCF复合物的亚基的细胞周期功能进行分析，并表征假定Slimb相互作用的中心体通路组件。我们的遗传分析将揭示slimb途径的其他组成部分，并开始阐明它们的功能。因为这种策略可以潜在地识别除了与Slimb直接接触的蛋白质之外的slimb途径的其他组分，所以我们的方法补充了SCF组分的生化纯化的现有努力。最后，随着Slimb影响中心体功能的机制取得进展，对其他中心体相关蛋白质的公正遗传筛选将为我们了解中心体在细胞分裂中的功能提供更多的拼图。这些发现将为预防或治疗癌症提供新的诊断或治疗靶点。