Ras protein signaling and the control of cell growth

描述（由申请人提供）：当条件不适合 细胞停止分裂，进入一个专门的休息期， 状态，在哺乳动物中称为G0，在细菌和酵母中称为静止期。 处于这些静止状态的细胞表现出增加的抵抗力， 环境压力，可以保持活力，虽然不分裂，非常 很长时间此外，这些时期之间的过渡 静止期和有丝分裂周期已被证明是关键点 增殖控制因此，对生物学的理解 静息细胞是一个基本的要求，一个完整的描述， 调控真核细胞增殖的机制。 这项建议的重点是管理进入固定资产的机制， 阶段在芽殖酵母，酿酒酵母。特别是 拟议的实验集中在一组突变体上，这些突变体在以下方面有缺陷： 稳定相进入。这些黑麦突变体鉴定出的几个基因 已发现编码RNA聚合酶（pol）II的重要调节因子 活动此外，对黑麦突变体的研究表明，RNA聚合酶II 活性受Ras蛋白信号通路控制。该信号 转导途径是大多数，如果不是全部， 真核生物有趣的是，这些Ras效应似乎是由 由上述RYE基因编码的蛋白质。因此，黑麦蛋白可能是 Ras信号传导和RNA pol II之间的重要联系， 生长和基因表达的适当协调。 上述工作提出了一种新的转录控制模式， 信号通路通过直接靶向蛋白质来调节基因表达 RNA聚合酶II全酶中。本提案将通过以下方式检验这一假设： 检查特定的黑麦蛋白是否确实是Ras的靶向蛋白 信号通路此外，拟议的实验将检查的作用， 黑麦蛋白在进入稳定期时的作用以及这些作用如何受到影响 通过Ras信号活性。最后，剩下的黑麦突变体将 以及进入后发生的基因表达变化 进入稳定期。总之，完成拟议的实验 应该提供Ras信号传导活性的作用， 稳定期的进入和生长控制的协调方式 与基因表达的调节有关。

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.