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XB-ART-46435
Cell Rep. January 31, 2013; 3 (1): 16-22.

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

Bontron S , Jaquenoud M , Vaga S , Talarek N , Bodenmiller B , Aebersold R , De Virgilio C .


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.

PubMed ID: 23273919
Article link: Cell Rep.

Genes referenced: mastl ptpa



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