REGULATION OF GROWTH AND PROLIFERATION BY DROSOPHILA TOR

果蝇对生长和增殖的调节

• 批准号: 6233071
• 负责人: Thomas P. Neufeld
• 金额: $ 25.57万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-01 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6233071
• 关键词: Drosophilidae; cell growth regulation; cell proliferation; cyclin dependent kinase; cyclins; drug resistance; enzyme activity; enzyme inhibitors; flow cytometry; immunofluorescence technique; phosphatidylinositol 3 kinase; phosphomonoesterases; protein kinase; sirolimus; transcription factor; western blottings

DESCRIPTION (applicant's description): The goal of this project is to understand the mechanisms that govern cell growth and proliferation during development. To this end, we propose genetic and molecular studies of dTOR, a Drosophila homolog of the yeast TOR and mammalian mTOR/FRAP protein kinases which have crucial roles in protein synthesis and cell cycle regulation. This project has four major aims. First, to determine how loss of dTOR activity results in cell cycle arrest, FACS analysis will be used to determine the cell cycle phases in which dTOR is required, and the activity and levels of candidate cell cycle regulators will be measured in dTOR mutant backgrounds. Second, we will determine the mechanisms by which dTOR signals to two of its well characterized targets, p70 S6 kinase and 4E-BP1. Third, we will use genetic and biochemical tests to determine how dTOR activity is regulated. We will distinguish between two alternative hypothesis: that dTOR is a target of the P13K signaling pathway, and that dTOR activity is regulated in response to nutrient levels. Fourth, these tests of candidate molecules will be complemented by genetic interaction screens aimed at identifying novel regulators and effectors of dTOR. We will screen for mutations that suppress dTOR phenotypes. The TOR protein and the growth pathways it regulates are highly conserved between flies and humans, and therefore we expect these studies to provide insights into growth control during human development, tissue homeostasis, and tumorigenesis.

描述（申请人的描述）：本项目的目标是 了解细胞生长和增殖的机制， 发展为此，我们建议对dTOR进行遗传和分子研究， 酵母TOR和哺乳动物mTOR/FRAP蛋白激酶的果蝇同源物 其在蛋白质合成和细胞周期调节中具有关键作用。这 项目有四大目标。首先，为了确定dTOR活性的丧失 导致细胞周期停滞，将使用FACS分析来确定细胞 需要dTOR的周期阶段，以及 将在dTOR突变体背景中测量候选细胞周期调节剂。 其次，我们将确定dTOR信号传导到两个细胞的机制。 充分表征的靶标，p70 S6激酶和4 E-BP 1。第三，我们将使用 基因和生物化学测试，以确定如何dTOR活性的调节。我们 将区分两个备择假设：dTOR是 P13 K信号通路，dTOR活性响应于 营养水平。第四，这些候选分子的测试将是 通过基因相互作用筛选， dTOR的调节子和效应子。我们会筛选出抑制 dTOR表型。TOR蛋白及其调节的生长途径是 在苍蝇和人类之间是高度保守的，因此我们认为 研究，以提供对人类发育过程中生长控制的见解， 组织稳态和肿瘤发生。