Orchestrated Action of PP2A Antagonizes Atg13 Phosphorylation and Promotes Autophagy after the Inactivation of TORC1

Yeasmin, Akter Mst; Waliullah, Talukdar Muhammad; Kondo, Akihiro; Kaneko, Atsuki; Koike, Nobuyuki; Ushimaru, Takashi

doi:10.1371/journal.pone.0166636

Cited by 48 publications

(36 citation statements)

References 57 publications

(67 reference statements)

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“…Furthermore, PP2A-type phosphatases are characterized as positive regulators of autophagy in mammals (Fujiwara et al 2016) and in Drosophila (Banreti et al 2012). In budding yeast, PP2A-type phosphatases have also been implicated in the dephosphorylation of Atg13 (Yeasmin et al 2016); however, the role of PP2Atype phosphatases on autophagy still remains under debate, as they were reported to be negative regulators of autophagy by another group (Yorimitsu et al 2009).…”

Section: Introductionmentioning

confidence: 99%

PP2C phosphatases promote autophagy by dephosphorylation of the Atg1 complex

Memisoglu

Eapen

Haber

2018

Preprint

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Autophagy is orchestrated by the Atg1-Atg13 complex in budding yeast. Under nutrient-rich conditions, Atg13 is maintained in a hyperphosphorylated state by TORC1 kinase. After nutrient starvation, Atg13 is dephosphorylated, triggering Atg1 kinase activity and autophagy induction.The phosphatases that dephosphorylate Atg13 remain uncharacterized. We show that two redundant PP2C phosphatases, Ptc2 and Ptc3, regulate autophagy via dephosphorylating both Atg13 and Atg1. In the absence of these phosphatases, starvation-induced macroautophagy is inhibited, as is the cytoplasm-to-vacuole targeting (Cvt) pathway, and the recruitment of the essential autophagy machinery to phagophore assembly sites (PAS) is impaired. Despite prolongation of the DNA damage-induced checkpoint in ptc2∆ ptc3∆ cells, genotoxin-induced autophagy is also blocked. Creating a genomic atg13-8SA allele under its endogenous promoter, lacking key TORC1 phosphorylation sites, bypasses the autophagy defect in ptc2D ptc3D strains.Taken together, these results imply that PP2C type phosphatases promote autophagy by regulating Atg1 complex.

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Section: Introductionmentioning

confidence: 99%

PP2C phosphatases promote autophagy by dephosphorylation of the Atg1 complex

Memisoglu

Eapen

Haber

2018

Preprint

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“…The phosphatase 2A complex (PP2A) subunits, Pph21p and Pph22p, decreased more their content in P29 than in flor yeast, especially at PCT1 (Figure 4). Studies have reported a role in autophagy regulation via TORC1 interaction [26]. Although Sec13p participates in vesicle trafficking The phosphatase 2A complex (PP2A) subunits, Pph21p and Pph22p, decreased more their content in P29 than in flor yeast, especially at PCT1 (Figure 4).…”

Section: Regulation Of Inductionmentioning

confidence: 94%

“…Although Sec13p participates in vesicle trafficking The phosphatase 2A complex (PP2A) subunits, Pph21p and Pph22p, decreased more their content in P29 than in flor yeast, especially at PCT1 (Figure 4). Studies have reported a role in autophagy regulation via TORC1 interaction [26]. Although Sec13p participates in vesicle trafficking as component of COPII vesicles, it has been recently reported a link between secretory pathway and autophagy [27] in which COPII vesicles fuse with Atg9p vesicles to provide membrane source and regulate the autophagosome abundance.…”

Section: Regulation Of Inductionmentioning

confidence: 99%

Autophagic Proteome in Two Saccharomyces cerevisiae Strains during Second Fermentation for Sparkling Wine Elaboration

et al. 2020

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A correlation between autophagy and autolysis has been proposed in order to accelerate the acquisition of wine organoleptic properties during sparkling wine elaboration. In this context, a proteomic analysis was carried out in two industrial Saccharomyces cerevisiae strains (P29, conventional sparkling wine strain and G1, implicated in sherry wine elaboration) with the aim of studying the autophagy-related proteome and comparing the effect of CO2 overpressure during sparkling wine elaboration. In general, a detrimental effect of pressure and second fermentation development on autophagy-related proteome was observed in both strains, although it was more pronounced in flor yeast strain G1. Proteins mainly involved in autophagy regulation and autophagosome formation in flor yeast G1, and those required for vesicle nucleation and expansion in P29 strain, highlighted in sealed bottle. Proteins Sec2 and Sec18 were detected 3-fold under pressure conditions in P29 and G1 strains, respectively. Moreover, ‘fingerprinting’ obtained from multivariate data analysis established differences in autophagy-related proteome between strains and conditions. Further research is needed to achieve more solid conclusions and design strategies to promote autophagy for an accelerated autolysis, thus reducing cost and time production, as well as acquisition of good organoleptic properties.

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“…Inactivation of TORC1 under starvation conditions triggers an autophagy response that is induced by the PP2A-dependent dephosphorylation of Atg13. Loss of PP2A, however, does not completely abrogate Atg13 dephosphorylation in yeast cells [122]. Interestingly, Atg13 contains different phosphorylation motifs, including four pSer-Pro sites that are preferentially targeted by Cdc14 [42,123].…”

Section: Cdc14 Phosphatase and The Defense Against Cellular Stressmentioning

confidence: 95%

The Multiple Roles of the Cdc14 Phosphatase in Cell Cycle Control

Manzano-López

Monje-Casas

2020

IJMS

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The Cdc14 phosphatase is a key regulator of mitosis in the budding yeast Saccharomyces cerevisiae. Cdc14 was initially described as playing an essential role in the control of cell cycle progression by promoting mitotic exit on the basis of its capacity to counteract the activity of the cyclin-dependent kinase Cdc28/Cdk1. A compiling body of evidence, however, has later demonstrated that this phosphatase plays other multiple roles in the regulation of mitosis at different cell cycle stages. Here, we summarize our current knowledge about the pivotal role of Cdc14 in cell cycle control, with a special focus in the most recently uncovered functions of the phosphatase.

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Orchestrated Action of PP2A Antagonizes Atg13 Phosphorylation and Promotes Autophagy after the Inactivation of TORC1

Cited by 48 publications

References 57 publications

PP2C phosphatases promote autophagy by dephosphorylation of the Atg1 complex

PP2C phosphatases promote autophagy by dephosphorylation of the Atg1 complex

Autophagic Proteome in Two Saccharomyces cerevisiae Strains during Second Fermentation for Sparkling Wine Elaboration

The Multiple Roles of the Cdc14 Phosphatase in Cell Cycle Control

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