Developmental Control of the Cell Cycle

细胞周期的发育控制

基本信息

批准号：
8098133
负责人：
Robert J Duronio
金额：
$ 29.41万
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/8098133
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 Coupled Cullin Proteins 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 G1/S Transition Gene Amplification Gene Expression Gene Targeting Genes Genetic Transcription Genome Growth Health Malignant Neoplasms Mediating Mitosis Modeling Molecular Normal Cell Organism Ovarian Follicle Pathway interactions Phenotype Play Polyploidy Process Proliferating Proteins Proteolysis Regulation Retinoblastoma Role S Phase S Phase Arrest Series Signal Transduction Staging Stem Cell Development Stimulus Testing Tissues Transactivation Transcription Coactivator Transcription Repressor/Corepressor Tumor Suppression Tumor Suppressor Proteins Variant member mutant novel paralogous gene programs 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对发育和肿瘤发生的理解至关重要。在发育过程中，细胞增殖是通过在细胞周期中与生长进行协调的进展来进行的。相反，细胞周期停滞发生在终末分化之前，通常是必需的。发育完成后，细胞增殖和细胞周期停滞也受到了高度调节：成年组织中的干细胞受到严格的细胞周期控制，而静态细胞也只能响应特定的刺激而增殖。在任何这些情况下，细胞周期控制的崩溃都会带来巨大的后果，并导致典型的癌症的失调生长。该项目的长期目标是阐明发展计划如何影响细胞周期的进程，这一过程仍然很少理解。在此提案中，我们关注控制G1-S转变的基因表达机制，因为这是大多数细胞决定输入还是退出细胞周期的时候。公共卫生相关性：细胞增殖是所有生物体生物学的一个基本方面，并且受到一系列高度精心策划的细胞生物事件的控制，称为细胞周期，该细胞周期指导基因组的准确重复和遗传。动物发育过程中细胞周期事件的详细分子描述对于我们对细胞增殖控制的理解至关重要，以及这种控制如何在癌症等疾病中出现问题。