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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.

SUBMITTER: Moreno-Torres M

PROVIDER: S-EPMC4579850 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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

Moreno-Torres Marta M Jaquenoud Malika M De Virgilio Claudio C

Nature communications 20150910

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 phosphorylati ...[more]

PMID: 26356805

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Dataset Information

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

Publications

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

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