Coupling of Protein Synthesis with Cell Division

蛋白质合成与细胞分裂的耦合

• 批准号: 10402935
• 负责人: MICHAEL S POLYMENIS
• 金额: $ 37.32万
• 依托单位: TEXAS A&M AGRILIFE RESEARCH
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-05-26 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10402935
• 关键词: Affect; Biochemical; Biological Models; Biological Process; Carbon; Cell Cycle; Cell Nucleus; Cell Proliferation; Cell division; Cells; Coupling; Data; Diffuse; Disease; Enzymes; Equipment and supply inventories; Fatty Acids; Folic Acid; Genetic; Goals; Growth; Hand; Isotopes; Knowledge; Light; Link; Lipids; Longevity; Measurement; Measures; Messenger RNA; Metabolic; Metabolic Control; Metabolic Pathway; Metabolism; Methylation; Mission; Mitosis; Mitotic; Molecular; Morphology; Nuclear; Nutrient; Output; Pathway interactions; Periodicity; Phenotype; Phosphatidylinositol Transfer Protein; Phospholipids; Physiological; Play; Positioning Attribute; Process; Property; Protein Biosynthesis; Proteome; Public Health; Purines; RNA; RNA-Binding Proteins; Research; Ribosomal Proteins; Ribosomes; Role; Saccharomycetales; Shapes; Testing; Time; Transact; Transcript; Translating; Translation Process; Translations; United States National Institutes of Health; Yeasts; amino acid metabolism; base; cell growth; experimental study; flexibility; grasp; instrument; lipid biosynthesis; lipid metabolism; lipid transfer protein; mutant; novel therapeutic intervention; nuclear division; protein metabolite; thymidylate

Protein synthesis governs if, how fast, and how many times cells divide. Yet how protein synthesis is linked molecularly with cell division is unknown. We will use budding yeast as a model system to answer this problem because yeast has unique properties suited for genetic and biochemical studies. In the previous period, we identified transcripts that engage with the protein synthesis machinery, the ribosomes, in the process of translation in synchronously dividing cells that maintained the physiological coupling of protein synthesis with their division. We will leverage these findings to tackle the long- standing problem of protein synthesis requirements for cell division. In Aim 1, we will identify how translational control of lipogenesis impinges on nuclear morphology. We propose experiments to test the idea that translational control of lipid synthesis, together with lipid-transfer proteins, impact specific parts of lipid metabolism, to control the morphology of the nucleus in the cell cycle. We will also measure the changing levels of lipids in the nucleus during cell division. In Aim 2, we will determine how outputs of one-carbon metabolic pathways change in the cell cycle and respond to translational control. Our data point to the critical roles of enzymes that are part of the folate-based, one-carbon metabolism. We will identify how protein synthesis controls the expression of enzymes of one-carbon metabolism. We will also measure how the different metabolite inputs and outputs of one-carbon metabolic pathways are allocated at distinct points in the cell cycle. Overall, the research we propose will reveal fundamental links between cell growth, protein synthesis, and cell division, enabling novel therapeutic interventions in proliferative diseases.

蛋白质合成决定细胞是否分裂、分裂的速度和次数。然而蛋白质合成是怎样的 与细胞分裂的分子关系尚不清楚。我们将使用芽殖酵母作为模型系统来回答 这个问题是因为酵母具有适合遗传和生化研究的独特特性。在 前一时期，我们鉴定了与蛋白质合成机制相关的转录本， 核糖体，在同步分裂的细胞中翻译过程中，维持生理学 蛋白质合成与其分裂的耦合。我们将利用这些发现来解决长期问题 细胞分裂所需的蛋白质合成需求是一个长期存在的问题。在目标 1 中，我们将确定如何 脂肪生成的翻译控制影响核形态。我们提出实验来测试 认为脂质合成的翻译控制与脂质转移蛋白一起影响特定部位 脂质代谢，控制细胞周期中细胞核的形态。我们还将测量 细胞分裂过程中细胞核中脂质水平的变化。在目标 2 中，我们将确定如何输出 一碳代谢途径在细胞周期中发生变化并对翻译控制做出反应。我们的数据 指出了酶的关键作用，这些酶是基于叶酸的一碳代谢的一部分。我们将 确定蛋白质合成如何控制一碳代谢酶的表达。我们将 还测量一碳代谢途径的不同代谢物输入和输出的情况 分配在细胞周期的不同点。总的来说，我们提出的研究将揭示基本原理 细胞生长、蛋白质合成和细胞分裂之间的联系，使新的治疗干预成为可能 增殖性疾病。