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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Blotting, Northern
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Cell Cycle Proteins / metabolism*
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Cyclin-Dependent Kinase Inhibitor Proteins / metabolism
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Cyclin-Dependent Kinases / metabolism
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Cyclins / metabolism
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Flow Cytometry
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G1 Phase Cell Cycle Checkpoints*
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Immunoblotting
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Immunoprecipitation
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Intercellular Signaling Peptides and Proteins
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Mechanistic Target of Rapamycin Complex 1
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Mitogen-Activated Protein Kinases / metabolism*
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Multiprotein Complexes / metabolism*
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Peptides
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Phosphorylation
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Protein Kinases / metabolism*
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Protein Phosphatase 2 / metabolism*
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Saccharomyces cerevisiae
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Saccharomyces cerevisiae Proteins / metabolism*
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TOR Serine-Threonine Kinases / metabolism*
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Ubiquitin-Protein Ligase Complexes / metabolism
Substances
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CDC55 protein, S cerevisiae
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Cell Cycle Proteins
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Cyclin-Dependent Kinase Inhibitor Proteins
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Cyclins
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Intercellular Signaling Peptides and Proteins
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Multiprotein Complexes
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Peptides
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SIC1 protein, S cerevisiae
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Saccharomyces cerevisiae Proteins
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endosulfine
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Ubiquitin-Protein Ligase Complexes
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Protein Kinases
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Rim15 protein, S cerevisiae
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Mechanistic Target of Rapamycin Complex 1
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TOR Serine-Threonine Kinases
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Cyclin-Dependent Kinases
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Mitogen-Activated Protein Kinases
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SLT2 protein, S cerevisiae
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Protein Phosphatase 2