A phosphorylation-independent role for the yeast cyclin-dependent kinase activating kinase Cak1.
Cdc28 is the main cyclin-dependent kinase (CDK) directing the cell cycle in the budding yeast Saccharomyces cerevisiae. Besides cyclin binding, Cdc28 requires phosphorylation by the Cak1 kinase to achieve full activity. We have previously isolated carboxy-terminal cdc28(CST) mutants that are temperature sensitive and exhibit high chromosome instability. Both phenotypes are suppressed by high copy Cak1 in a manner that is independent of its catalytic activity and conversely, combination of cdc28(CST) and cak1 mutations results in synthetic lethality. Altogether, these results suggest that for the Cdc28 complexes to remain stable and active, an interaction with Cak1 is needed via the carboxyl terminus of Cdc28. We report two-hybrid assay data that support this model, and results that indicate that actively growing yeast cells require an optimum Cdc28:Cak1 ratio. While Cak1 is constitutively active and expressed, dividing cells tightly regulate Cak1 protein levels to ensure presence of adequate levels of Cdc28 CDK activity.
Kim
Su-Hwa
SH
Department of Biochemistry and Cellular and Molecular Biology, The University of Tennessee, Knoxville, Tennessee, USA.
Gadiparthi
Keerthi
K
Kron
Stephen J
SJ
Kitazono
Ana A
AA
D001665:Binding Sites / Q000235:genetics; D017489:CDC28 Protein Kinase, S cerevisiae / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle; D018844:Cyclin-Dependent Kinases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D004795:Enzyme Stability; D018628:Gene Dosage; D005800:Genes, Fungal; D046912:Multiprotein Complexes; D009154:Mutation; D010766:Phosphorylation; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology* / Q000235:genetics* / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D000095043:Cyclin-Dependent Kinase-Activating Kinase
D046912:Multiprotein Complexes; D029701:Saccharomyces cerevisiae Proteins; D017489:CDC28 Protein Kinase, S cerevisiae; D018844:Cyclin-Dependent Kinases; D000095043:Cyclin-Dependent Kinase-Activating Kinase