How are the yeast cyclins, PCL6 and PCL7 regulated in the GLC7 pathway? [abstract]

Abstract

The eukaryotic Protein Phosphatase 1 (PP1) is a serine/threonine phosphatase that is encoded by the essential gene, GLC7, in Saccharomyces cerevisiae (budding yeast). The Glc7 protein is involved in the regulation of multiple cellular processes including mitosis and meiosis. A range of regulatory subunits controls the activity of Glc7 by influencing its intracellular localization and substrate specificity. Reduction of Glc7/PP1 activity halts the cell cycle in metaphase to correct errors because faithful chromosome segregation depends on the opposing activity of Glc7 protein phosphatase and Ipl1/Aurora protein kinase. We have identified the Glc7 pathway that controls cell division however; the components of this pathway are not fully understood. Glc7 is conditionally activated by phospho-Glc8, the cyclin dependent kinase, Pho85 (Cdk5), associated with Pcl6 and Pcl7 (two of its ten cyclins). Our knowledge about these two cyclins is limited. Our goal was to understand how these cyclin are regulated in the Glc7 pathway. We have studied the stability of Pcl6 and Pcl7 as well as the in vivo activity of Pcl6 and Pcl7. Elongin C, a component of the Nucleotide Excision Repair Factor (NEF4) has been reported to affect the stability of Pcl6. We have confirmed this finding. We found that Elc1 and subunits of two Elc1 complexes are required for wild-type stability of Pcl6 and Pcl7. Furthermore, compared to Pcl6, Pcl7 is a relatively unstable cell cycle regulated protein with greatest levels in G1.