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，该酶对出芽酵母的细胞周期执行至关重要。我们已经证明Cdc14p的磷酸酶活性是细胞周期进程所必需的。遗传证据表明，Cdc14p是有丝分裂退出所必需的，但Cdc14p的底物和功能尚未明确。我们的长期目标是确定Cdc14p在细胞周期调节中的重要作用，并确定其活性是如何被调节的。研究人员建议鉴定Cdcl4p的底物，并确定Cdc14p活性在整个细胞周期中受到控制的机制。初步发现已经确定了Cdc14p调节因子或磷酸化底物的候选蛋白，这将是我们研究的主要重点。这些信息将增加我们对有丝分裂退出所需的关键事件的理解。因为控制细胞周期的机制在整个进化过程中是高度保守的，这些酵母的研究对于理解人类细胞的增殖是如何被控制的也很有价值。编码调节细胞周期的蛋白质的基因是癌症突变的常见目标。破译控制细胞周期进程的调控途径可以提供重要的信息，了解这一过程在转化细胞中是如何出错的，并可以确定阻止它们生长的潜在靶点。

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.