Regulation of the Pcl7-Pho85 cyclin-cdk complex by Pho81

Saccharomyces cerevisiae strains lacking a functional Pho85 cyclin-dependen t kinase (cdk) exhibit a complex phenotype, including deregulation of phosp hatase genes controlled by the transcription factor Pho4, slow growth on ri ch media, failure to grow using galactose, lactate or glycerol as a carbon source and hyperaccumulation of glycogen. The ability of Pho85 to regulate the transcription factor Pho4 is mediated by its association the Pho80 cycl in. Some other regulatory functions of the Pho85 cdk have been shown to be mediated via its interaction with a recently identified family of Pho80-rel ated cyclins (Pcls). Here, we show that the poorly characterized Pho80-like protein Pcl7 forms a functional kinase complex with the Pho85 cdk, and tha t the activity of this complex is inhibited in response to phosphate starva tion. Additionally, we show that Pcl7 interacts with the phosphate-regulate d cyclin-cdk inhibitor Pho81, and that the regulation of the Pcl7-Pho85 com plex in response to changes in phosphate levels is dependent on Pho81. Thus , we demonstrate for the first time that the Pho81 regulator is not dedicat ed to regulating Pho80, but may act to co-ordinate the activity of both the Pho80-Pho85 and Pcl7-Pho85 cyclin-cdk complexes in response to phosphate l evels. We also demonstrate that expression of Pcl7 is cell cycle regulated, with maximal activity occurring in mid to late S-phase, perhaps suggesting a role for Pcl7 in cell cycle progression. Finally, we describe the phenot ype of pcl7 Delta and pcl6 Delta yeast strains that have defects in carbon source utilization.