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。不同尺寸和形状的产生需要 调节生长的量和位置，以及生长与细胞周期的协调。的 细胞在细胞周期中调节和协调生长的机制很差， 明白我们工作的重点是使用芽殖酵母作为模型系统，以了解细胞生长 与细胞周期相协调。很可能芽殖酵母用来协调 生长与细胞周期的关系与所有真核细胞都有关。此外，这些机制是潜在的 新药物的目标是阻止癌细胞的增殖。 总结 在芽殖酵母中，一个新的子细胞的生长在G1期通过细胞周期蛋白依赖的 激酶1（Cdk 1）。据认为，Cdk 1通过激活高度保守的 信号模块，包括Cdc 42 GTTON。Cdk 1激活细胞凋亡的分子机制 cdc 42信号传导模块仍然是难以捉摸的。在我们的初步研究中，我们已经表明， Cdc 42信号传导模块的组分是Cdk 1的直接靶点。该提案的一个主要目标是 测试这些蛋白质的磷酸化代表Cdk 1活性与 新细胞生长的开始。 第二个细胞周期蛋白依赖性激酶Pho 85也在G1期细胞生长的启动中起作用; 然而，控制细胞生长的Pho 85的下游靶标知之甚少。我们的初步 研究表明，Shs 1 septin是Pho 85的重要和直接靶点。而且我们 鉴定了一个Pho 85依赖的信号网络，该网络是调节细胞生长所必需的。第二 该提案的主要目标是验证Pho 85对Shs 1的磷酸化是 pho 85依赖的信号网络。我们还将描述其他蛋白质的作用， 网络中的功能。

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.