Yeast endosulfines control entry into quiescence and chronological life span by inhibiting protein phosphatase 2A

Bontron, Séverine; Jaquenoud, Malika; Vaga, Stefania; Talarek, Nicolas; Bodenmiller, Bernd; Aebersold, Ruedi; De Virgilio, Claudio

doi:10.1016/j.celrep.2012.11.025

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Yeast endosulfines control entry into quiescence and chronological life span by inhibiting protein phosphatase 2A

Bontron, Séverine Department of Biology, Division of Biochemistry, University of Fribourg, Switzerland
Jaquenoud, Malika Department of Biology, Division of Biochemistry, University of Fribourg, Switzerland
Vaga, Stefania Institute of Molecular Systems Biology, ETH Zürich, Switzerland
Talarek, Nicolas Department of Biology, Division of Biochemistry, University of Fribourg, Switzerland
Bodenmiller, Bernd Institute of Molecular Systems Biology, ETH Zürich, Switzerland
Aebersold, Ruedi Institute of Molecular Systems Biology, ETH Zürich, Switzerland
De Virgilio, Claudio Department of Biology, Division of Biochemistry, University of Fribourg, Switzerland

27.12.2012

Published in:

Cell Reports. - 2012, vol. 3, no. 1, p. 16–22

English 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.

Faculty

Faculté des sciences et de médecine

Department

Département de Biologie

Language