ROLE OF THE ANTIZYME FAMILY DURING XENOPUS DEVELOPMENT

抗酶家族在非洲爪蟾发育过程中的作用

• 批准号: 7609960
• 负责人: Charles Richard Toth
• 金额: $ 2.38万
• 依托单位: UNIVERSITY OF RHODE ISLAND
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7609960
• 关键词: Anabolism; Binding; Catabolism; Cell Proliferation; Cells; Charge; Complement; Computer Retrieval of Information on Scientific Projects Database; Development; Disease; Enzymes; Family; Funding; Genes; Genetic Screening; Grant; Institution; Nature; Organism; Ornithine Decarboxylase; Pathway interactions; Phenotype; Play; Polyamines; Process; Proteins; Rate; Reaction; Regulation; Research; Research Personnel; Resources; Role; Saccharomyces cerevisiae; Saccharomycetales; Source; Toxic effect; United States National Institutes of Health; Xenopus; Yeasts; design; ornithine decarboxylase antizyme; uptake; yeast genetics

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Polyamines are charged organic molecules that are vitally important for macromolecular reactions in cells but are toxic at high levels. There exist well-regulated biosynthetic pathways for both polyamine anabolism and catabolism. A protein involved in the control of polyamine levels, antizyme (AZ), plays a role in regulating polyamine levels in cells. AZ lowers polyamines below toxic levels by inhibiting polyamine uptake and activity of the rate-limiting enzyme ornithine decarboxylase (ODC) via direct binding and targeted degradation of ODC. By understanding the function of AZ in a normal setting, one can better understand the role of AZ in a disease setting and determine the nature of its toxicity in controlling cell proliferation. A tractable organism for polyamine research is the budding yeast Saccharomyces cerevisiae. The regulation of polyamine synthesis in yeast has been delineated although not specifically the role of antizyme in the process. In addition, mammalian forms of the polyamine genes can complement their functional equivalents in yeast cells. Using a yeast genetic screen, genes that functionally interact with AZ and its regulation of ODC can be isolated and characterized. This study proposes to use a genetic screen to obtain yeast genes that play a role in the regulation and function of the ODC/AZ pathway in yeast. A strain has been designed that is dependent on ODC enzymatic activity for viability. Expression of antizyme results in induced lethality due to lowered levels of polyamines. We hope to isolate yeast genes that can interact with the polyamine pathway and revert the lethal phenotype.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 多胺是带电的有机分子，对细胞中的大分子反应至关重要，但在高水平上具有毒性。 对于多胺代谢和分解代谢，存在良好调节的生物合成途径。 参与多胺水平抗酶（AZ）的蛋白质在调节细胞中多胺水平方面起作用。 AZ通过抑制多胺摄取和限速酶鸟氨酸脱羧酶（ODC）的活性，通过直接结合和靶向ODC的靶向降解来降低毒性水平。 通过了解AZ在正常环境中的功能，可以更好地理解AZ在疾病环境中的作用，并确定其毒性在控制细胞增殖中的性质。 用于多胺研究的可疗法的生物是酿酒酵母的萌芽酵母菌。 酵母中多胺合成的调节已被描述，尽管并非具体地在此过程中的作用。 另外，多胺基因的哺乳动物形式可以补充其在酵母细胞中的功能等效物。 使用酵母遗传筛选，可以分离和表征与AZ功能相互作用的基因及其ODC的调节。 这项研究建议使用遗传筛选获得酵母基因，该基因在酵母中ODC/AZ途径的调节和功能中发挥作用。 已经设计了一种菌株，取决于ODC酶促活性的生存能力。 抗酶的表达导致由于多胺水平降低引起的致死性。 我们希望分离可以与多胺途径相互作用并恢复致命表型的酵母基因。