FUNCTION AND REGULATION OF THE CDC14 PROTEIN PHOSPHATASE

CDC14 蛋白磷酸酶的功能和调节

• 批准号: 6651164
• 负责人: HARRY CHARBONNEAU
• 金额: $ 24.26万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-05-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6651164
• 关键词: Saccharomyces cerevisiae; cell cycle; cell cycle proteins; enzyme activity; enzyme induction /repression; fungal genetics; fungal proteins; intermolecular interaction; laboratory rabbit; microorganism culture; phosphoprotein phosphatase

The CDC14 gene of Saccharomyces cerevisiae encodes a dual specificity phosphatase that is essential for the execution of the cell cycle in the budding yeast. We have shown that the phosphatase activity of Cdc14p is required for cell cycle progression. Genetic evidence suggests that Cdc14p is needed for exit from mitosis, but the substrates and function of Cdc14p have not been defined. Our long term goal is to identify the essential role that Cdc14p plays in cell cycle regulation and to determine how its activity is regulated. Studies are proposed to identify substrates for Cdcl4p and to define the mechanism(s) by which Cdc14p activity is controlled throughout the cell cycle. Preliminary findings have identified proteins that are candidates for regulators or phosphosubstrates of Cdc14p and these will be a major focus of our studies. This information will increase our understanding of the key events required for exit from mitosis. Because the mechanisms controlling the cell cycle are highly conserved throughout evolution, these studies in yeast will also be valuable in understanding how the proliferation of human cells is controlled. Genes encoding proteins that regulate the cell cycle are common targets for mutation in cancer. Deciphering the regulatory pathways that control cell cycle progression can provide important information about how this process goes awry in transformed cells and can identify potential targets for blocking their growth.

酿酒酵母的Cdc14基因编码双重特异性磷酸酶，这对于在发芽酵母中执行细胞周期至关重要。 我们已经表明，CDC14P的磷酸酶活性是细胞周期进程所必需的。 遗传证据表明，从有丝分裂中退出需要Cdc14p，但是尚未定义Cdc14p的底物和功能。 我们的长期目标是确定CDC14P在细胞周期调节中起的重要作用，并确定其活性的调节方式。 提出了研究以鉴定CDCL4P的底物，并定义在整个细胞周期中控制CDC14P活性的机制。初步发现已经确定了蛋白质，这些蛋白质是CDC14P调节剂或磷酸覆盖物的候选者，这将是我们研究的主要重点。 这些信息将增加我们对退出有丝分裂所需的关键事件的理解。由于控制细胞周期的机制在整个演化过程中都高度保守，因此这些酵母中的研究也将在理解人类细胞的增殖方面有价值。 编码调节细胞周期的蛋白质的基因是癌症突变的常见靶标。 解释控制细胞周期进程的调节途径可以提供有关该过程如何在转化的细胞中出现问题的重要信息，并可以识别阻断其生长的潜在靶标。