Yeast Ess1, a Conserved PPlase Essential for Mitosis

酵母 Ess1，有丝分裂必需的保守 Pplase

• 批准号: 6766774
• 负责人: Steven D. HANES
• 金额: $ 22.85万
• 依托单位: WADSWORTH CENTER
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6766774
• 关键词: DNA directed RNA polymerase; Saccharomyces cerevisiae; alleles; carboxyl group; cell cycle; cell growth regulation; enzyme activity; flow cytometry; fungal genetics; gene expression; gene interaction; gene mutation; genetic regulation; immunofluorescence technique; laboratory rabbit; microarray technology; molecular cloning; peptidylprolyl isomerase; phenotype; polymerase chain reaction; protein structure function; regulatory gene; virulence; western blottings; yeast two hybrid system

DESCRIPTION (APPLICANT'S ABSTRACT): The long-term goal is to understand how prolyl-isomerases (PPIases) control important cellular processes such as transcription and mitosis. These enzymes catalyze the cis/trans isomerization of the peptide bond that precedes the cyclic amino acid proline. This conformational change is thought to be important for proper folding of proteins and control of their activity. PPIases are found in all organisms, and are best known because they are the targets of immunosuppressive and antifungal drugs. However, their normal function in cells is not understood, since most can be removed by gene deletion in their respective organism without observable consequences. There is one exception, however, a PPIase called Ess 1 that is required for growth in the yeast, Saccharomyces cerevisiae. Ess 1 and its human homolog, Pin 1, are implicated in cell cycle confrol. Recent discoveries show that Ess 1 interacts physically and genetically with the carboxy-terminal domain (CTD) of RNA polymerase II, suggesting a role in transcription of cell cycle genes. This study will take advantage of the essential nature of Ess 1 and the power of yeast genetics to elucidate the Ess1 pathway. The main focus will be to understand the role of Essi in transcription. Specifically, the aims are: (1) to define genetic interactions between the ESS1 gene and genes that are known to be important for transcription, (2) to discover genes whose transcription depends on Ess1 and that control cell cycle progression through mitosis, (3) to combine the use of yeast genetics with biochemistry to study how Ess1 binds the CTD, with the goal of determining how Ess1 controls RNA polymerase II function, and finally, (4) to examine the importance of Ess1 for virulence in pathogenic fungi, with the eventual goal of developing antifungal drugs that inhibit Ess1 function.

描述（申请人摘要）：长期目标是了解 脯氨酰异构酶（PPI酶）控制重要的细胞过程， 转录和有丝分裂。这些酶催化顺/反异构化 在环状氨基酸脯氨酸之前的肽键。这 构象变化被认为对蛋白质的正确折叠是重要的 控制他们的活动。PPIase存在于所有生物体中， 因为它们是免疫抑制和抗真菌药物的靶点。 然而，它们在细胞中的正常功能尚不清楚，因为大多数都可以被 在各自的生物体中通过基因缺失去除， 后果然而，有一个例外，称为Ess 1的PPIase， 在酿酒酵母中生长所必需的。ESS 1及其人 同源物Pin 1与细胞周期调控有关。最近的发现表明 Ess 1在物理上和遗传上与 结构域（CTD）的RNA聚合酶II，这表明在转录的细胞 周期基因这项研究将利用Ess 1的本质 以及酵母遗传学对阐明EST 1途径的能力。主要的重点 就是理解埃西在转录中的作用。具体而言，目标 （1）确定ESS 1基因和以下基因之间的遗传相互作用： 已知对转录很重要，（2）发现 转录依赖于BMP 1，并控制细胞周期进程， （3）将酵母遗传学与生物化学联合收割机结合起来进行研究 BMP 1如何结合CTD，目的是确定BMP 1如何控制RNA 聚合酶II的功能，最后，（4）检查的重要性， 致病真菌的毒力，最终目标是开发抗真菌药物 抑制BMP 1功能的药物。