Mechanisms controlling cell cycle exit upon terminal differentiation
终末分化时控制细胞周期退出的机制
基本信息
- 批准号:8402603
- 负责人:
- 金额:$ 23.3万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2008
- 资助国家:美国
- 起止时间:2008-12-01 至 2013-12-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAwardB-LymphocytesBiochemicalBiological ModelsCancer cell lineCancerousCandidate Disease GeneCell Culture SystemCell Culture TechniquesCell CycleCell Cycle RegulationCell LineCell divisionCellsCoupledDevelopmentDrosophila eyeDrosophila genusEffector CellEyeFutureGenesGeneticGenetic EpistasisGenetic ScreeningGoalsGrantHumanIn VitroInstructionMalignant NeoplasmsMammalian CellMammalsOrthologous GenePathway interactionsPhasePhenotypePost-Transcriptional RegulationProcessProliferatingRNA InterferenceResearchRoleSignal PathwaySignal TransductionSystemTestingTissuesWingWorkbasecancer therapyexperienceflyinsightmature animalnoveloverexpressionpreventtool
项目摘要
Terminal differentiation is often coupled with permanent exit from the cell cycle and represents the most
common cellular state in adult animals. Yet it remains unclear how proliferation is blocked in differentiated
tissues. The goal of this project is to determine how terminal differentiation signals impinge on the cell cycle
machinery to induce a stable quiescent state and investigate how this state is disrupted in cancer. In the
research proposed here, I use a combination of genetic and biochemical approaches in Drosophila and
mammalian cells to delineate the conserved genetic pathways that control cell cycle exit. During the K99
phase of this grant, I investigated the redundant mechanisms that limit cycling in differentiated Drosophila
tissues, obtained experience working with 2 different mammalian cell lines that can be induced to
differentiate in vitro for future studies of cell cycle exit, and worked on a screen to identify genes that when
overexpressed or inhibited by RNAi, de-regulate the cell cycle to cause ectopic proliferation in contexts of
terminal differentiation. Such genes would normally be activated or inhibited upon terminal differentiation, but
likely become de-regulated in cancers. During the ROO phase of the award, I will determine the precise
mechanisms by which these genes regulate the cell cycle (Aim 1) and examine the roles of mammalian
orthologs of these genes in normal and cancerous mammalian cells (Aim2). I will also investigate the
signaling pathways by which these genes are regulated, using genetic epistasis tools in both Drosophila and
mammalian cells (Aim 3). Such work will begin to delineate the conserved pathways connecting terminal
differentiation signals with cell cycle controls, and determine how they can become de-regulated leading to
cancer.
终末分化通常伴随着细胞周期的永久退出,并且代表了最
成年动物的常见细胞状态。然而,目前尚不清楚分化细胞中的增殖是如何被阻止的。
组织。该项目的目标是确定终末分化信号如何影响细胞周期
诱导稳定静止状态的机制并研究这种状态在癌症中如何被破坏。在
在这里提出的研究,我在果蝇中结合使用遗传和生化方法
哺乳动物细胞描绘了控制细胞周期退出的保守遗传途径。 K99期间
在这笔资助的阶段,我研究了限制分化果蝇循环的冗余机制
组织,获得了使用 2 种不同的哺乳动物细胞系的经验,这些细胞系可以被诱导
体外分化以用于细胞周期退出的未来研究,并进行了筛选以识别当
过表达或被 RNAi 抑制,解除细胞周期的调节,导致细胞异位增殖
终端分化。这些基因通常会在终末分化时被激活或抑制,但是
在癌症方面可能会放松管制。在奖励的原产地组织阶段,我将确定准确的
这些基因调节细胞周期的机制(目标 1)并检查哺乳动物的作用
这些基因在正常和癌性哺乳动物细胞中的直系同源物(Aim2)。我也会调查
使用果蝇和果蝇中的遗传上位工具来调节这些基因的信号传导途径
哺乳动物细胞(目标 3)。此类工作将开始描绘连接终端的保守路径
细胞周期控制的分化信号,并确定它们如何解除管制,从而导致
癌症。
项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
States of G0 and the proliferation-quiescence decision in cells, tissues and during development.
- DOI:10.1387/ijdb.160343lb
- 发表时间:2017
- 期刊:
- 影响因子:0
- 作者:Dan Sun;Laura A. Buttitta
- 通讯作者:Dan Sun;Laura A. Buttitta
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Laura A Buttitta其他文献
Laura A Buttitta的其他文献
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{{ truncateString('Laura A Buttitta', 18)}}的其他基金
Mechanisms controlling cell cycle exit upon terminal differentiation
终末分化时控制细胞周期退出的机制
- 批准号:
8181834 - 财政年份:2008
- 资助金额:
$ 23.3万 - 项目类别:
Mechanisms controlling cell cycle exit upon terminal differentiation
终末分化时控制细胞周期退出的机制
- 批准号:
8206617 - 财政年份:2008
- 资助金额:
$ 23.3万 - 项目类别:
Mechanisms controlling cell cycle exit upon terminal differentiation
终末分化时控制细胞周期退出的机制
- 批准号:
7569698 - 财政年份:2008
- 资助金额:
$ 23.3万 - 项目类别:
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