Protein Kinase C Regulates Late Cell Cycle-Dependent Gene Expression

The control of the cell cycle in eukaryotes is exerted in part by the coordinated action of a series of transcription factor complexes. This is exemplified by the Mcm1p-Fkh2p-Ndd1p complex in Saccharomyces cerevisiae, which controls the cyclical expression of the CLB2 cluster of genes at the G(2)/M phase transition. The activity of this complex is positively controlled by cyclin-dependent kinase (CDK) and polo kinases. Here, we demonstrate that the protein kinase Pkc1p works in the opposite manner to inhibit the activity of the Mcm1p-Fkh2p-Ndd1p complex and the expression of its target genes. In particular, Pkc1p causes phosphorylation of the coactivator protein Ndd1p. Reductions in Pkc1p activity and the presence of Pkc1p-insensitive Ndd1p mutant proteins lead to changes in the timing of CLB2 cluster expression and result in associated late cell cycle defects. This study therefore identifies an important role for Pkc1p in controlling the correct temporal expression of genes in the cell cycle.