The TORC1 and PKA protein kinases are central elements of signaling networks that regulate eukaryotic cell proliferation in response to growth factors and/or nutrients. In yeast, attenuation of signaling by these kinases following nitrogen and/or carbon limitation activates the protein kinase Rim15, which orchestrates the initiation of a reversible cellular quiescence program to ensure normal chronological life span. The molecular elements linking Rim15 to distal readouts including the expression of Msn2/4- and Gis1-dependent genes involve the endosulfines Igo1/2. Here, we show that Rim15, analogous to the greatwall kinase in Xenopus, phosphorylates endosulfines to directly inhibit the Cdc55-protein phosphatase 2A (PP2A(Cdc55)). Inhibition of PP2A(Cdc55) preserves Gis1 in a phosphorylated state and consequently promotes its recruitment to and activation of transcription from promoters of specific nutrient-regulated genes. These results close a gap in our perception of and delineate a role for PP2A(Cdc55) in TORC1-/PKA-mediated regulation of quiescence and chronological life span.
|Evidence ID||Analyze ID||Interactor||Interactor Systematic Name||Interactor||Interactor Systematic Name||Type||Assay||Annotation||Action||Modification||Phenotype||Source||Reference||Note|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Gene Ontology Term||Gene Ontology Term ID||Qualifier||Aspect||Method||Evidence||Source||Assigned On||Annotation Extension||Reference|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Phenotype||Experiment Type||Experiment Type Category||Mutant Information||Strain Background||Chemical||Details||Reference|
|Evidence ID||Analyze ID||Regulator||Regulator Systematic Name||Target||Target Systematic Name||Experiment||Assay||Construct||Conditions||Strain Background||Reference|