title: Yeast endosulfines control entry into quiescence and chronological life span by inhibiting protein phosphatase 2A.
abstract: 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.
authors.affiliation: Department of Biology, Division of Biochemistry, University of Fribourg, 1700 Fribourg, Switzerland.
authors.forename: Séverine
authors.initials: S
authors.lastname: Bontron
authors.forename: Malika
authors.initials: M
authors.lastname: Jaquenoud
authors.forename: Stefania
authors.initials: S
authors.lastname: Vaga
authors.forename: Nicolas
authors.initials: N
authors.lastname: Talarek
authors.forename: Bernd
authors.initials: B
authors.lastname: Bodenmiller
authors.forename: Ruedi
authors.initials: R
authors.lastname: Aebersold
authors.forename: Claudio
authors.initials: C
authors.lastname: De Virgilio
mesh_terms: D000595:Amino Acid Sequence; D036341:Intercellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D040901:Proteomics; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D020123:Sirolimus / Q000494:pharmacology; D013194:Staining and Labeling
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D029701:Saccharomyces cerevisiae Proteins; C075663:endosulfine; D054648:Protein Phosphatase 2; D020123:Sirolimus