Moreno-Torres, Marta Jaquenoud, Malika De Virgilio, Claudio 2015-09-10 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. application/pdf https://folia.unifr.ch/global/documents/304548 https://folia.unifr.ch/documents/304548/files/dev_tcg.pdf https://folia.unifr.ch/documents/304548/files/dev_tcg_sm.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1038/ncomms9256 info:eu-repo/semantics/openAccess License undefined Nature Communications. - 2015, vol. 6, p. 8256 info:eu-repo/classification/udc/57 TORC1 controls G1-S cell cycle transition in yeast via Mpk1 and the greatwall kinase pathway http://purl.org/coar/resource_type/c_6501