Ras protein signaling and the control of cell growth

描述(由申请人提供)：当条件不是最佳时 继续生长，细胞停止分裂，进入专门的休眠状态 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对 环境压力，并可以保持生存，尽管不是分裂，非常 很长一段时间。此外，这两个时期之间的过渡 静止期和有丝分裂周期被证明是 增殖控制。因此，对生物的生物学的理解 休眠细胞是完整描述 真核细胞增殖的调控机制。 这项建议的重点是管理进入静止状态的机制。 在萌芽酵母阶段，酿酒酵母。尤其是， 拟议的实验集中在一组有缺陷的突变体上 固定相进入。这些黑麦突变体鉴定出的几个基因 已被发现编码重要的RNA聚合酶(POL)II调节因子 活动。此外，对黑麦突变体的研究表明，rna polII 活性受RAS蛋白信号通路控制。这个信号 转导通路是大多数(如果不是全部)细胞生长的关键调节因子。 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，黑麦蛋白质可能是 RAS信号和RNA PolII之间的重要联系，允许 适当协调生长和基因表达。 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 在RNA PolII全酶中。这项提议将通过以下方式检验这一假设 研究特定的黑麦蛋白是否确实是RAS的靶标 信号通路。此外，拟议的实验将检查这些角色 黑麦蛋白质在静止相的进入以及这些作用是如何受到影响的 受RAS信号活动的影响。最后，剩下的黑麦突变体将是 特征以及在进入时发生的基因表达变化 进入静止状态。总之，拟议中的实验的完成 应提供对RAS信号活动在 进入静止阶段和协调生长控制的方式 基因表达的调控。

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.