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.