title: Glucose regulation of Saccharomyces cerevisiae cell cycle genes.
abstract: Nutrient-limited Saccharomyces cerevisiae cells rapidly resume proliferative growth when transferred into glucose medium. This is preceded by a rapid increase in CLN3, BCK2, and CDC28 mRNAs encoding cell cycle regulatory proteins that promote progress through Start. We have tested the ability of mutations in known glucose signaling pathways to block glucose induction of CLN3, BCK2, and CDC28. We find that loss of the Snf3 and Rgt2 glucose sensors does not block glucose induction, nor does deletion of HXK2, encoding the hexokinase isoenzyme involved in glucose repression signaling. Rapamycin blockade of the Tor nutrient sensing pathway does not block the glucose response. Addition of 2-deoxy glucose to the medium will not substitute for glucose. These results indicate that glucose metabolism generates the signal required for induction of CLN3, BCK2, and CDC28. In support of this conclusion, we find that addition of iodoacetate, an inhibitor of the glyceraldehyde-3-phosphate dehydrogenase step in yeast glycolysis, strongly downregulates the levels CLN3, BCK2, and CDC28 mRNAs. Furthermore, mutations in PFK1 and PFK2, which encode phosphofructokinase isoforms, inhibit glucose induction of CLN3, BCK2, and CDC28. These results indicate a link between the rate of glycolysis and the expression of genes that are critical for passage through G(1).
authors.affiliation: Department of Biomolecular Chemistry, University of Wisconsin, Madison, Wisconsin 53705, USA.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Newcomb
authors.forename: Jasper A
authors.initials: JA
authors.lastname: Diderich
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Slattery
authors.forename: Warren
authors.initials: W
authors.lastname: Heideman
mesh_terms: D017489:CDC28 Protein Kinase, S cerevisiae / Q000096:biosynthesis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics; D004734:Energy Metabolism / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015966:Gene Expression Regulation, Fungal / Q000235:genetics*; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D009154:Mutation / Q000235:genetics; D010732:Phosphofructokinase-1 / Q000235:genetics; D025481:Phosphofructokinase-2 / Q000235:genetics; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: C082733:BCK2 protein, S cerevisiae; C079895:CLN3 protein, S cerevisiae; D018797:Cell Cycle Proteins; D016213:Cyclins; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D025481:Phosphofructokinase-2; D010732:Phosphofructokinase-1; D017489:CDC28 Protein Kinase, S cerevisiae; D005947:Glucose