REGULATION OF GROWTH AND PROLIFERATION BY DROSOPHILA TOR

果蝇对生长和增殖的调节

• 批准号: 6520407
• 负责人: Thomas P. Neufeld
• 金额: $ 25.44万
• 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/6520407
• 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）：该项目的目的是 了解控制细胞生长和增殖的机制 发展。为此，我们提出了DTOR的遗传和分子研究 酵母和哺乳动物MTOR/FRAP蛋白激酶的果蝇同源物 在蛋白质合成和细胞周期调节中具有关键作用。这 项目有四个主要目标。首先，确定DTOR活动的损失 细胞周期停滞的结果，FACS分析将用于确定细胞 需要DTOR的循环阶段，以及 候选细胞周期调节剂将在DTOR突变背景中进行测量。 其次，我们将确定DTOR信号到其中两个的机制 特征良好的靶标，P70 S6激酶和4E-BP1。第三，我们将使用 遗传和生化测试以确定如何调节DTOR活性。我们 将区分两个替代假设：DTOR是 p13k信号通路和该DTOR活性受到调节 营养水平。第四，这些候选分子测试将是 旨在识别新颖的遗传相互作用筛选的补充 DTOR的监管机构和效应子。我们将筛选抑制的突变 DTOR表型。 Tor蛋白质及其调节的生长途径是 在苍蝇和人类之间高度保守，因此我们期望这些 研究在人类发展过程中提供对增长控制的见解， 组织稳态和肿瘤发生。