Ras protein signaling and the control of cell growth

Ras 蛋白信号传导和细胞生长的控制

• 批准号: 6459208
• 负责人: Paul K Herman
• 金额: $ 26.86万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6459208
• 关键词: DNA directed RNA polymerase; Saccharomyces cerevisiae; biological signal transduction; cell cycle proteins; cell growth regulation; fungal genetics; gene expression; gene mutation; guanine nucleotide binding protein; phosphorylation; protein kinase A

DESCRIPTION (provided by applicant): When conditions are not optimal for continued growth, cells stop dividing and enter into a specialized resting state, known as G0 in mammals and stationary phase in bacteria and yeasts. Cells in these quiescent states exhibit an increased resistance to environmental stress and can remain viable, although not dividing, for very long periods of time. Moreover, the transitions between these periods of quiescence and the mitotic cycle have been shown to be key points of proliferative control. Therefore, an understanding of the biology of the resting cell is an essential requirement for a complete description of the mechanisms governing eukaryotic cell proliferation. This proposal is focused on the mechanisms regulating the entry into stationary phase in the budding yeast, Saccharomyces cerevisiae. In particular, the proposed experiments focus on a collection of mutants that are defective for stationary phase entry. Several of the genes identified by these rye mutants have been found to encode important regulators of RNA polymerase (pol) II activity. Moreover, studies of the rye mutants have suggested that RNA pol II activity is controlled by the Ras protein signaling pathway. This signal transduction pathway is a key regulator of cell growth in most, if not all, eukaryotes. Interestingly, these Ras effects appear to be mediated by the proteins encoded by the above RYE genes. Therefore, the Rye proteins could be an essential link between Ras signaling and RNA pol II that allows for the proper coordination of growth and gene expression. The above work has suggested a novel mode of transcriptional control whereby signaling pathways regulate gene expression by directly targeting proteins within the RNA pol II holoenzyme. This proposal will test this hypothesis by examining whether particular Rye proteins are indeed targeted by the Ras signaling pathway. In addition, the proposed experiments will examine the roles of the Rye proteins in stationary phase entry and how these roles are affected by Ras signaling activity. Finally, the remaining rye mutants will be characterized as well as the gene expression changes that occur upon the entry into stationary phase. In all, the completion of the proposed experiments should provide insights into the role of Ras signaling activity during stationary phase entry and the manner in which growth control is coordinated with the regulation of gene expression.

描述（由申请人提供）：条件不是最佳的 持续生长，细胞停止分裂并进入专门的休息 状态，在哺乳动物中被称为G0，在细菌和酵母菌中被称为固定期。 这些静态状态中的细胞表现出对 环境压力，尽管没有分裂，但仍可以保持可行 长时间。此外，这些时期之间的过渡 静态和有丝分裂周期已显示为 增殖控制。因此，对生物学的理解 休息单元是完整描述的必不可少的要求 控制真核细胞增殖的机制。 该提案的重点是调节进入固定的机制 萌芽的酵母中的相位，酿酒酵母。特别是 拟议的实验集中于一个有缺陷的突变体的集合 固定相进入。这些黑麦突变体鉴定的几个基因 已经发现编码RNA聚合酶（POL）II的重要调节剂 活动。此外，对黑麦突变体的研究表明RNA POL II 活性由RAS蛋白信号通路控制。这个信号 转导途径是大多数（即使不是全部）的细胞生长的关键调节剂 真核生物。有趣的是，这些RAS效应似乎是由 由上述黑麦基因编码的蛋白质。因此，黑麦蛋白可能是 RAS信号传导与RNA POL II之间的基本联系，该联系允许 适当地协调生长和基因表达。 上述工作提出了一种新颖的转录控制方式 信号通路通过直接靶向蛋白来调节基因表达 在RNA Pol II Holoenzyme中。该建议将通过 检查特定的黑性黑性蛋白是否确实是RAS的靶向 信号通路。此外，提出的实验将检查角色 在固定相进入中的黑麦蛋白以及这些角色如何影响 通过RAS信号活动。最后，其余的黑麦突变体将是 特征和基因表达在进入时发生的变化 进入固定阶段。总的来说，提出的实验的完成 应该提供有关RAS信号活动在期间的作用的见解 固定相位进入及其协调生长控制的方式 与基因表达的调节。