FUNCTION AND REGULATION OF THE CDC14 PROTEIN PHOSPHATASE

酿酒酵母的CDC14基因编码一种双特异性磷酸酶，它对芽期酵母细胞周期的执行是必不可少的。我们已经证明了CDC14P的磷酸酶活性是细胞周期进程所必需的。遗传学证据表明，CDC14P是退出有丝分裂所必需的，但其底物和功能尚未确定。我们的长期目标是确定CDC14P在细胞周期调控中的重要作用，并确定其活性是如何调节的。有人建议进行研究，以确定cdcl4p的底物，并确定cdc14p在整个细胞周期中被控制的机制(S)。初步的发现已经确定了作为CDC14P的调节剂或磷酸底物的候选蛋白质，这些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进化过程中是高度保守的，这些对酵母的研究对于理解人类细胞的增殖是如何控制的也将是有价值的。编码调节细胞周期的蛋白质的基因是癌症中常见的突变目标。破译控制细胞周期进程的调控途径可以提供关于转化细胞中这一过程如何出错的重要信息，并可以确定阻止其生长的潜在靶点。

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.