Control of Cell Cycle Events by Cyclin-Dependent Kinases

相关性 细胞在大小和形状上表现出非凡的多样性。生成不同的大小和形状需要 调节生长的数量和位置，以及生长与细胞周期的协调。这个 细胞在细胞周期背景下调节和协调生长的机制很差 明白了。我们的工作重点是使用发芽酵母作为一个模型系统来了解细胞如何生长 与细胞周期相协调。很可能是萌芽酵母用来协调 生长与细胞周期有关，与所有真核细胞有关。此外，这些机制是潜在的 旨在阻止癌细胞增殖的新药靶点。 摘要 在萌芽酵母中，新的子代细胞的生长在G1期由依赖于细胞周期蛋白的活性启动。 蛋白激酶1(CDK1)。据认为，CDK1通过激活高度保守的 包括CDC42 GTP酶的信号模块。CDK1激活细胞外信号通路的分子机制 CDC42信号模块仍然难以捉摸。在我们的初步研究中，我们已经证明了 CDC42信号模块的组件是CDK1的直接靶标。这项提议的一个主要目标是 验证以下假设：这些蛋白的磷酸化代表CDK1活性和 启动新的细胞生长。 第二个细胞周期蛋白依赖的激酶，称为Pho85，也在启动G1期细胞生长过程中发挥作用； 然而，控制细胞生长的Pho85下游靶点却知之甚少。我们的预赛 研究表明，Shs1 Septin是Pho85的一个重要和直接的靶标。此外，我们有 发现了一个依赖于Pho85的信号网络，这是调节细胞生长所必需的。第二 这项提议的主要目标是检验这样一种假设，即Pho85对Shs1的磷酸化是 依赖于Pho85的信令网络。我们还将对其他蛋白质的作用进行表征 在网络中发挥作用。

Relevance Cells show extraordinary diversity in size and shape. Generation of diverse sizes and shapes requires regulation of the amount and location of growth, as well as coordination of growth with the cell cycle. The mechanisms by which cells regulate and coordinate growth in the context of the cell cycle are poorly understood. The focus of our work is to use budding yeast as a model system to understand how cell growth is coordinated with the cell cycle. It is likely that the mechanisms used by budding yeast to coordinate growth with the cell cycle are relevant to all eukaryotic cells. In addition, these mechanisms are potential targets for new drugs aimed at blocking the proliferation of cancer cells. Summary In budding yeast, growth of a new daughter cell is initiated in G1 by the activity of cyclin-dependent kinase 1 (Cdk1). It is thought that Cdk1 initiates growth of a new cell by activating a highly conserved signaling module that includes the Cdc42 GTPase. The molecular mechanisms by which Cdk1 activates the Cdc42 signaling module have remained elusive. In our preliminary studies, we have shown that key components of the Cdc42 signaling module are direct targets of Cdk1. A major goal of this proposal is to test the hypothesis that phosphorylation of these proteins represents a direct link between Cdk1 activity and the initiation of new cell growth. A second cyclin-dependent kinase called Pho85 also plays a role in initiation of cell growth in G1; however the downstream targets of Pho85 that control cell growth are poorly understood. Our preliminary studies suggest that the Shs1 septin is an important and direct target of Pho85. Moreover, we have identified a Pho85-dependent signaling network that is required for regulation of cell growth. The second major goal of this proposal is to test the hypothesis that phosphorylation of Shs1 by Pho85 is a critical step in the Pho85-dependent signaling network. We will also characterize the roles of additional proteins that function in the network.