Regulation of the Pcl7-Pho85 cyclin-cdk complex by Pho81.
Saccharomyces cerevisiae strains lacking a functional Pho85 cyclin-dependent kinase (cdk) exhibit a complex phenotype, including deregulation of phosphatase genes controlled by the transcription factor Pho4, slow growth on rich 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 cyclin. Some other regulatory functions of the Pho85 cdk have been shown to be mediated via its interaction with a recently identified family of Pho80-related cyclins (Pcls). Here, we show that the poorly characterized Pho80-like protein Pcl7 forms a functional kinase complex with the Pho85 cdk, and that the activity of this complex is inhibited in response to phosphate starvation. Additionally, we show that Pcl7 interacts with the phosphate-regulated cyclin-cdk inhibitor Pho81, and that the regulation of the Pcl7-Pho85 complex in response to changes in phosphate levels is dependent on Pho81. Thus, we demonstrate for the first time that the Pho81 regulator is not dedicated 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 levels. 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 phenotype of pcl7Delta and pcl6Delta yeast strains that have defects in carbon source utilization.
Lee
M
M
Eukaryotic Transcription Laboratory, Marie Curie Research Institute, The Chart, Oxted, Surrey RH8 OTL, UK.
O'Regan
S
S
Moreau
J L
JL
Johnson
A L
AL
Johnston
L H
LH
Goding
C R
CR
D000595:Amino Acid Sequence; D002453:Cell Cycle; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010641:Phenotype; D010710:Phosphates / Q000378:metabolism; D012097:Repressor Proteins; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins
D016213:Cyclins; D004791:Enzyme Inhibitors; D005656:Fungal Proteins; C066824:PHO80 protein, S cerevisiae; C081227:PHO81 protein, S cerevisiae; D010710:Phosphates; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D018844:Cyclin-Dependent Kinases; C058605:PHO85 protein, S cerevisiae