title: TORC1 controls G1-S cell cycle transition in yeast via Mpk1 and the greatwall kinase pathway.
abstract: The target of rapamycin complex 1 (TORC1) pathway couples nutrient, energy and hormonal signals with eukaryotic cell growth and division. In yeast, TORC1 coordinates growth with G1-S cell cycle progression, also coined as START, by favouring the expression of G1 cyclins that activate cyclin-dependent protein kinases (CDKs) and by destabilizing the CDK inhibitor Sic1. Following TORC1 downregulation by rapamycin treatment or nutrient limitation, clearance of G1 cyclins and C-terminal phosphorylation of Sic1 by unknown protein kinases are both required for Sic1 to escape ubiquitin-dependent proteolysis prompted by its flagging via the SCF(Cdc4) (Skp1/Cul1/F-box protein) ubiquitin ligase complex. Here we show that the stabilizing phosphorylation event within the C-terminus of Sic1 requires stimulation of the mitogen-activated protein kinase, Mpk1, and inhibition of the Cdc55 protein phosphatase 2A (PP2A(Cdc55)) by greatwall kinase-activated endosulfines. Thus, Mpk1 and the greatwall kinase pathway serve TORC1 to coordinate the phosphorylation status of Sic1 and consequently START with nutrient availability.
authors.affiliation: Department of Biology, University of Fribourg, Chemin du Musée 10, Fribourg CH-1700, Switzerland.
authors.forename: Marta
authors.initials: M
authors.lastname: Moreno-Torres
authors.affiliation: Department of Biology, University of Fribourg, Chemin du Musée 10, Fribourg CH-1700, Switzerland.
authors.forename: Malika
authors.initials: M
authors.lastname: Jaquenoud
authors.affiliation: Department of Biology, University of Fribourg, Chemin du Musée 10, Fribourg CH-1700, Switzerland.
authors.forename: Claudio
authors.initials: C
authors.lastname: De Virgilio
mesh_terms: D015152:Blotting, Northern; D018797:Cell Cycle Proteins / Q000378:metabolism*; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D005434:Flow Cytometry; D059585:G1 Phase Cell Cycle Checkpoints; D015151:Immunoblotting; D047468:Immunoprecipitation; D036341:Intercellular Signaling Peptides and Proteins; D000076222:Mechanistic Target of Rapamycin Complex 1; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000378:metabolism*; D010455:Peptides; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism
chemical_list: C071246:CDC55 protein, S cerevisiae; D018797:Cell Cycle Proteins; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D016213:Cyclins; D036341:Intercellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; D010455:Peptides; C086926:SIC1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C075663:endosulfine; D043743:Ubiquitin-Protein Ligase Complexes; D011494:Protein Kinases; C410736:Rim15 protein, S cerevisiae; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D018844:Cyclin-Dependent Kinases; D020928:Mitogen-Activated Protein Kinases; C072724:SLT2 protein, S cerevisiae; D054648:Protein Phosphatase 2