ANCHORAGE INDEPENDENT GROWTH INDUCED BY CDC42

拟议研究的基本假设是， 活化的Cdc42诱导锚定非依赖性生长的能力来源于 对cyclin A的影响。因此，建议的重点是确定 Cdc42诱导锚定非依赖性生长的机制以及它如何 刺激细胞周期蛋白A的表达。应用 有三个具体目标。第一个将是确定机制， 其中Cdc42激活细胞周期蛋白A启动子。这里的目标是确定 并描述了顺式和反式作用因子， Cdc42对细胞周期蛋白A启动子的反应性。第二个目标是确定 负责介导细胞周期蛋白A诱导的Cdc42效应物， 非锚定生长第三个目标是确定是否 Cdc42V12效应子是粘附依赖性信号的关键介质， 正常的增殖反应这些实验的重要性在于 确定转化Cdc42突变体是否使用类似的途径， 正常生理条件下的野生型Cdc 42。

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.