GENETIC CHARACTERIZATION OF TWO GENES INVOLVED IN YEAST PROGRAMMED CELL DEATH

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 程序性细胞死亡(PCD)是多细胞生物体中重要的生理过程和重要的抗肿瘤防御机制。有些人甚至将逃避程序性细胞死亡的能力称为“癌症的标志”。酿酒酵母是研究包括PCD在内的后生动物细胞复杂生理过程的有用模型。人们在试图描述驱动细胞程序性死亡的分子机制方面做了大量工作。在过去的四年里，我在普罗维登斯学院的实验室一直在研究UTH1和BXI1，这两个基因与酵母细胞程序性死亡有关。我们已经产生了缺乏UTH1和BXI1的突变体，并表明它们具有分别与细胞壁和未折叠蛋白反应相联系的表型。这一建议概述了识别UTH1和BXI1功能所涉及的分子途径的遗传策略。它将利用酵母系统作为程序性细胞死亡的模型系统相对于哺乳动物系统的主要优势：酵母细胞可以进行遗传分析，使研究人员能够快速确定生物过程背后的分子路径。本提案中描述的遗传策略将寻求澄清酵母中UTH1、BXI1和其他PCD基因之间的遗传关系，以确定调节该生物体中程序性细胞死亡的分子途径。鉴于不同物种间细胞凋亡途径的显著保守性，这一分析应该会进一步深入了解包括人类在内的高等生物的类似过程。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Programmed cell death (PCD) is both an important physiological process and a significant anti-tumor defense mechanism in multicellular organisms. Some have even called the ability to evade programmed cell death a "hallmark of cancer". The budding yeast, Saccharomyces cerevisiae, has served as a useful model for complex physiological processes of metazoan cells including PCD. Much work has gone into attempting to describe the molecular mechanisms that drive programmed cell death. For the past four years, my laboratory at Providence College has studied UTH1 and BXI1, two genes linked with programmed cell death in yeast. We have generated mutants lacking UTH1 and BXI1 and have shown that they have phenotypes linking them to the cell wall and the unfolded protein response respectively. This proposal outlines genetic strategies to identify the molecular pathways involved in UTH1 and BXI1 function. It will exploit the primary advantage of the yeast system over its mammalian counterpart as a model system for programmed cell death: Yeast cells are amenable to genetic analysis that allows investigators to identify rapidly molecular pathways underlying a biological process. The genetic strategies described in this proposal will seek to clarify the genetic relationships between UTH1, BXI1, and other PCD genes in yeast to identify the molecular pathways that regulate programmed cell death in this organism. Given the remarkable conservation of the apoptotic pathways across diverse species, this analysis should lead to further insights into the analogous processes in higher organisms including human beings.