TORC1 controls G1-S cell cycle transition in yeast via Mpk1 and the greatwall kinase pathway.

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.
Mesh Terms:
Blotting, Northern, Cell Cycle Proteins, Cyclin-Dependent Kinase Inhibitor Proteins, Cyclin-Dependent Kinases, Cyclins, Flow Cytometry, G1 Phase Cell Cycle Checkpoints, Immunoblotting, Immunoprecipitation, Mitogen-Activated Protein Kinases, Multiprotein Complexes, Peptides, Phosphorylation, Protein Kinases, Protein Phosphatase 2, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, TOR Serine-Threonine Kinases, Ubiquitin-Protein Ligase Complexes
Nat Commun
Date: Sep. 12, 2015
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