Developmental Control of the Cell Cycle

细胞周期的发育控制

基本信息

批准号：
7729391
负责人：
Robert J Duronio
金额：
$ 30.01万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-01-01 至 2013-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7729391
关键词：
Acceleration Address Adult Affect Animals Apoptosis Binding Biological Biology Cell Cycle Cell Cycle Arrest Cell Cycle Progression Cell Cycle Regulation Cell Proliferation Cells Cyclin-Dependent Kinases Cyclins DNA Binding DNA biosynthesis DNA replication origin Development Diploid Cells Disease Drosophila genus E2F Transcription Factor 1 E2F1 gene Embryo Embryonic Development Event Failure Family G1 Arrest G1 Phase Gene Amplification Gene Expression Gene Targeting Genes Genetic Transcription Genome Growth Malignant Neoplasms Mediating Mitosis Modeling Molecular Normal Cell Organism Ovarian Follicle Pathway interactions Phase Phenotype Play Polyploidy Process Proliferating Proteins Proteolysis Regulation Retinoblastoma Role Series Signal Transduction Staging Stem Cell Development Stimulus Testing Tissues Transactivation Transcription Coactivator Tumor Suppression Tumor Suppressor Proteins Variant member mutant novel paralogous gene programs public health relevance response transcription factor tumorigenesis ubiquitin ligase ubiquitin-protein ligase

项目摘要

DESCRIPTION (provided by applicant): Determining the mechanisms of normal cell cycle control is critical for our understanding of both development and oncogenesis. During development, cell proliferation occurs by coordinating progress through the cell cycle with growth. Conversely, cell cycle arrest occurs prior to, and is often necessary for, terminal differentiation. Cell proliferation and cell cycle arrest are also highly regulated after the completion of development: stem cells in adult tissues are under tight cell cycle control, as are quiescent cells that only proliferate in response to particular stimuli. Breakdowns in cell cycle control in any of these circumstances can have drastic consequences and contribute to the deregulated growth typical of cancer. The long term objective of this project is to elucidate how developmental programs affect cell cycle progression, a process that remains poorly understood. In this proposal we focus on gene expression mechanisms that control the G1-S transition because this is when most cells decide whether to enter or to exit the cell cycle. PUBLIC HEALTH RELEVANCE: Cell proliferation is a fundamental aspect of the biology of all organisms, and is controlled by a highly orchestrated series of cell biological events termed the cell cycle that directs the accurate duplication and inheritance of the genome. A detailed molecular description of cell cycle events during animal development is critical for our understanding of cell proliferation control, and how such control goes awry in diseases like cancer.

描述（由申请人提供）：确定正常细胞周期控制的机制对于我们理解发育和肿瘤发生至关重要。在发育过程中，细胞增殖是通过协调细胞周期的进展与生长而发生的。相反，细胞周期停滞发生在终末分化之前，并且通常是终末分化所必需的。细胞增殖和细胞周期停滞在发育完成后也受到高度调控：成体组织中的干细胞受到严格的细胞周期控制，就像仅在响应特定刺激时增殖的静止细胞一样。在任何这些情况下，细胞周期控制的破坏都会产生严重的后果，并导致癌症典型的生长失调。该项目的长期目标是阐明发育程序如何影响细胞周期进程，而这一过程目前仍知之甚少。在这个提案中，我们重点关注控制 G1-S 转变的基因表达机制，因为这是大多数细胞决定是否进入或退出细胞周期的时候。公共健康相关性：细胞增殖是所有生物体生物学的一个基本方面，并受到一系列高度精心策划的细胞生物学事件（称为细胞周期）的控制，细胞周期指导着基因组的精确复制和遗传。对动物发育过程中细胞周期事件的详细分子描述对于我们理解细胞增殖控制以及这种控制在癌症等疾病中如何出错至关重要。