Cell Cycle Control in Early Drosophila Development

果蝇早期发育中的细胞周期控制

基本信息

批准号：
7919726
负责人：
Terry L. ORR-WEAVER
金额：
$ 10.92万
依托单位：
WHITEHEAD INSTITUTE FOR BIOMEDICAL RES
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-02-01 至 2010-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7919726
关键词：
Affect Animal Model CDC2 Protein Kinase Cell Cycle Cell Cycle Regulation Cell Proliferation Chromosome Segregation Complex Cues Cyclic AMP-Dependent Protein Kinases Cyclin B Cyclins DNA biosynthesis Development Drosophila genus Embryo Embryonic Development Family member Female Fertilization Funding Genes Genetic Genetic Transcription Germ Cells Goals Haploidy Human Infertility Investigation Lead Link Malignant Neoplasms Mediating Meiosis Mitosis Mitotic Modeling Oocytes Organ Model Organism Orthologous Gene Phosphotransferases Play Ploidies Production Proteins Proteolysis Recovery Regulation Regulator Genes Role Signal Transduction Translations Ubiquitin Variant blastomere structure cell growth gene function genetic regulatory protein insight male mutant prevent protein degradation response

Affect Animal Model CDC2 Protein Kinase Cell Cycle Cell Cycle Regulation Cell Proliferation Chromosome Segregation Complex Cues Cyclic AMP-Dependent Protein Kinases Cyclin B Cyclins DNA biosynthesis Development Drosophila genus Embryo Embryonic Development Family member Female Fertilization Funding Genes Genetic Genetic Transcription Germ Cells Goals Haploidy Human Infertility Investigation Lead Link Malignant Neoplasms Mediating Meiosis Mitosis Mitotic Modeling Oocytes Organ Model Organism Orthologous Gene Phosphotransferases Play Ploidies Production Proteins Proteolysis Recovery Regulation Regulator Genes Role Signal Transduction Translations Ubiquitin Variant blastomere structure cell growth gene function genetic regulatory protein insight male mutant prevent protein degradation response

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项目摘要

DESCRIPTION (provided by applicant): During development multicellular organisms must coordinate differentiation with cell proliferation, and the cell cycle is modified to achieve particular developmental goals. The regulation of two variant cell cycles is being investigated using Drosophila as a model: meiosis, a modified cell cycle in which two rounds of chromosome segregation permit the production of haploid gametes, and a rapid cell cycle used during early embryogenesis. The meiotic cell cycle is subject to developmental control to coordinate progression through meiosis with oocyte differentiation and fertilization. Understanding the control circuitry for these cycles will provide insights into causes of human infertility, and the regulatory genes identified are likely to be important in preventing cancer. Drosophila is an ideal model organism for the discovery of gene function because of the ready link between mutant recovery and protein identification. Cell cycle control genes identified in Drosophila most often have orthologs that play essential roles in humans. A protein kinase complex, PAN GU, drives the embryonic cycles by controlling translation of Cyclin B, a key protein that when complexed with the CDK1 kinase subunit promotes mitosis and inhibits DNA replication. The mechanism by which PAN GU regulates Cyclin B translation will be defined, elucidating the role of translational control in triggering the onset of mitosis. In the previous funding period mutants defective in controlling the meiotic cell cycle were recovered. Two of the affected proteins appear to be necessary for ubiquitin-mediated protein degradation. Their mechanisms of action will be determined and protein targets identified. This will reveal the role of protein degradation in meiotic chromosome segregation and lead to the identification of proteins critical for meiosis. The protein products of other genes necessary for the completion of meiosis and the restart of the cell cycle at fertilization will be isolated.

描述（由申请人提供）：在开发过程中，多细胞生物必须与细胞增殖协调分化，并修改细胞周期以实现特定的发育目标。正在使用果蝇作为模型研究了两个变体细胞周期的调节：减数分裂，修饰的细胞周期，其中两轮染色体分离允许产生单倍体配子，以及在早期胚胎发生期间使用的快速细胞周期。减数分裂细胞周期受发育控制，以通过减数分裂与卵母细胞分化和受精进行协调。了解这些周期的控制电路将提供有关人类不育症原因的见解，并且所鉴定的调节基因可能在预防癌症中很重要。果蝇是发现基因功能的理想模型生物，因为突变恢复与蛋白质鉴定之间存在现成的联系。在果蝇中鉴定出的细胞周期控制基因通常具有直系同源物在人类中起重要作用。蛋白激酶复合物Pan Gu通过控制细胞周期蛋白B的翻译来驱动胚胎周期，这是一种关键蛋白质，当与CDK1激酶酶复合时，该蛋白会促进有丝丝并抑制DNA的复制。 PAN GU调节细胞周期蛋白B翻译的机制将被定义，从而阐明了转化控制在触发有丝分裂发作中的作用。在前一个资金期间，在控制减数分裂细胞周期方面有缺陷的突变体。两种受影响的蛋白似乎对于泛素介导的蛋白质降解是必需的。将确定它们的作用机理并确定蛋白质靶标。这将揭示蛋白质降解在减数分裂染色体分离中的作用，并导致对减数分裂至关重要的蛋白质的鉴定。将分离出对减数分裂所必需的其他基因的蛋白质产物和受精时的细胞周期重新开始。