ROLE OF THE ANTIZYME FAMILY DURING XENOPUS DEVELOPMENT

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 多胺是带电的有机分子，对细胞中的大分子反应至关重要，但在高水平下是有毒的。多胺合成代谢和分解代谢都存在调控良好的生物合成途径。参与控制多胺水平的一种蛋白质，抗酶(AZ)，在调节细胞中的多胺水平方面发挥作用。AZ通过直接结合和靶向降解鸟氨酸脱羧酶(ODC)来抑制多胺的摄取和限速酶鸟氨酸脱羧酶(ODC)的活性，从而将多胺降低到毒性水平以下。通过了解AZ在正常情况下的功能，人们可以更好地了解AZ在疾病发生中的作用，并确定其在控制细胞增殖方面的毒性性质。多胺研究的易驯化生物是萌芽酵母酿酒酵母。酵母中多胺合成的调节已经被描述，尽管没有特别说明抗酶在这一过程中的作用。此外，哺乳动物形式的多胺基因可以在酵母细胞中补充其功能等价物。利用酵母遗传筛选，可以分离和鉴定与AZ及其对ODC的调节功能相互作用的基因。这项研究建议使用遗传筛选来获得在酵母中ODC/AZ途径的调节和功能中发挥作用的酵母基因。该项目的目标是：(1)通过遗传筛选确定AZ在酿酒酵母增殖中的功能作用。这个目标将被用来检验以下假设：AZ通过控制ODC水平来调节细胞的增殖能力。

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. The goal of the project is: (1) determine the functional role that AZ plays in proliferation in Saccharomyces cerevisiae by a genetic screen. The goal will be used to test the following hypothesis: AZ regulates the proliferative capacity of cells by controlling ODC levels.