ANCHORAGE INDEPENDENT GROWTH INDUCED BY CDC42

拟议研究的基本假设是 活化的CdC42诱导非锚定生长的能力来自于 它对周期蛋白A的影响因此，该提案的重点是确定 CdC42诱导非锚定生长的机制及其机制 在没有丝裂原的情况下刺激细胞周期蛋白A的表达。应用程序 包含三个具体目标。第一个是通过以下方式确定机制 哪个CDC42激活了细胞周期蛋白A启动子。这里的目标将是确定 并描述了顺式和反式作用因素的特征 CDC42-对细胞周期蛋白A启动子的响应。第二个目标是确定 CDC42效应器，负责介导细胞周期蛋白A的诱导和 锚地--独立增长。第三个目标将是确定是否 CDC42V12效应器是黏附依赖信号的关键介体 正常的增殖反应。这些实验的重要性在于 确定转化的Cdc42突变体是否使用类似的途径 野生型CDC42在正常生理条件下。

The underlying hypothesis of the proposed studies is that the ability of activated Cdc42 to induce anchorage-independent growth derives from its effects on cyclin A. Thus, the proposal focuses on identifying the mechanisms by which Cdc42 induces anchorage-independent growth and how it stimulates cyclin A expression in the absence of mitogens. The application contains three specific aims. The first will be to determine the mechanism by which Cdc42 activates the cyclin A promoter. Here the goal will be to identify and characterize the cis- and trans-acting factors that confer Cdc42-responsiveness to the cyclin A promoter. The second aim is to identify Cdc42 effectors that are responsible for mediating cyclin A induction and anchorage-independent growth. The third aim will be to establish whether Cdc42V12 effectors are critical mediators of adhesion-dependent signals during the normal proliferative response. The importance of these experiments is to establish whether similar pathways are used by a transforming Cdc42 mutant and wild type Cdc42 under normal physiological conditions.