title: The Yeast Cyclin-Dependent Kinase Routes Carbon Fluxes to Fuel Cell Cycle Progression.
abstract: Cell division entails a sequence of processes whose specific demands for biosynthetic precursors and energy place dynamic requirements on metabolism. However, little is known about how metabolic fluxes are coordinated with the cell division cycle. Here, we examine budding yeast to show that more than half of all measured metabolites change significantly through the cell division cycle. Cell cycle-dependent changes in central carbon metabolism are controlled by the cyclin-dependent kinase (Cdk1), a major cell cycle regulator, and the metabolic regulator protein kinase A. At the G1/S transition, Cdk1 phosphorylates and activates the enzyme Nth1, which funnels the storage carbohydrate trehalose into central carbon metabolism. Trehalose utilization fuels anabolic processes required to reliably complete cell division. Thus, the cell cycle entrains carbon metabolism to fuel biosynthesis. Because the oscillation of Cdk activity is a conserved feature of the eukaryotic cell cycle, we anticipate its frequent use in dynamically regulating metabolism for efficient proliferation.
authors.affiliation: Department of Biology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Ewald
authors.affiliation: Institute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland; PhD Program Systems Biology, Life Science Zurich Graduate School, 8057 Zurich, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kuehne
authors.affiliation: Institute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Nicola
authors.initials: N
authors.lastname: Zamboni
authors.affiliation: Department of Biology, Stanford University, Stanford, CA 94305, USA. Electronic address: skotheim@stanford.edu.
authors.forename: Jan M
authors.initials: JM
authors.lastname: Skotheim
mesh_terms: D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism*; D017489:CDC28 Protein Kinase, S cerevisiae / Q000235:genetics / Q000378:metabolism*; D002244:Carbon / Q000378:metabolism*; D002453:Cell Cycle; D049109:Cell Proliferation; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004261:DNA Replication; D004271:DNA, Fungal / Q000096:biosynthesis / Q000235:genetics; D004734:Energy Metabolism; D004789:Enzyme Activation; D059585:G1 Phase Cell Cycle Checkpoints; D010766:Phosphorylation; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014198:Trehalase / Q000378:metabolism; D014199:Trehalose / Q000378:metabolism
chemical_list: D004271:DNA, Fungal; D029701:Saccharomyces cerevisiae Proteins; D002244:Carbon; D014199:Trehalose; D017868:Cyclic AMP-Dependent Protein Kinases; D016203:CDC2 Protein Kinase; D017489:CDC28 Protein Kinase, S cerevisiae; C000614366:NTH1 protein, S cerevisiae; D014198:Trehalase