ANCHORAGE INDEPENDENT GROWTH INDUCED BY CDC42

CDC42 带来的安克雷奇独立增长

• 批准号: 6633392
• 负责人: Margaret Mary Chou
• 金额: $ 29.2万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6633392
• 关键词: cell adhesion; cell growth regulation; cell proliferation; cyclins; gene induction /repression; genetic promoter element; genetic regulatory element; guanine nucleotide binding protein; protooncogene; tissue /cell culture; transcription factor

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.

拟议研究的基本假设是 活化的 Cdc42 诱导不依赖贴壁生长的能力源自 它对细胞周期蛋白 A 的影响。因此，该提案的重点是确定 Cdc42 诱导锚定非依赖性生长的机制及其如何 在没有丝裂原的情况下刺激细胞周期蛋白 A 的表达。应用 包含三个具体目标。首先是确定机制 其中 Cdc42 激活细胞周期蛋白 A 启动子。这里的目标是确定 并描述了赋予的顺式和反式作用因子 Cdc42 对细胞周期蛋白 A 启动子的响应性。第二个目标是确定 Cdc42 效应子负责介导细胞周期蛋白 A 的诱导和 不依赖锚定的生长。第三个目标是确定是否 Cdc42V12 效应器是粘附依赖性信号的关键介体 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，以及 正常生理条件下的野生型Cdc42。