Cdc14 Phosphatase Promotes TORC1-Regulated Autophagy in Yeast

Protein phosphatases of Saccharomyces cerevisiae

“…In fact, there are as many as 455 potential substrates for Cdc14 (Kao et al, 2014). Cdc14 is involved in a number of functions, including chromosome segregation (MatosPerdomo and Machin, 2018;Ramos et al, 2017), autophagy induction (Kondo et al, 2018), recombinational DNA repair (Villoria et al, 2017), cytokinesis (Kuilman et al, 2015;Miller et al, 2015), and spindle stability and duplication (Fox et al, 2017;Villoria et al, 2017). Cdc14 is activated in times of starvation and has been connected to TORC1 inactivation (Villoria et al, 2017).…”

The Multiple Roles of the Cdc14 Phosphatase in Cell Cycle Control

“…Cdc14 sequential action impedes new rounds of DNA and SPB duplication until the subsequent cell cycle, promotes cell cycle arrest when the DNA is damaged, facilitates DNA repair by collaborating in the tethering of DSBs to the SPBs, orchestrates rDNA and telomere condensation to ease their segregation during mitosis, and plays a key role in cytokinesis (Figure 1). Additionally, the Cdc14 phosphatase integrates different signaling pathways to coordinate cell cycle progression in response to different types of cellular stresses and environmental cues, such as the cell-wall integrity, the HOG, the pheromone-response, or the filamentous growth signaling pathways [54], and also has the capacity to trigger autophagy under starvation stress [42], which is especially relevant for yeast adaptation to environmental changes once the cell cycle is initiated (Figure 1). Numerous studies demonstrate that many of these functions, if not all, are extraordinarily conserved among the Cdc14 homologues during evolution.…”

“…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]. Accordingly, cdc14-1 cells display a hyper-phosphorylated Atg13 profile, both in normal conditions and under starvation, whereas Cdc14 overexpression or its premature nuclear release by expression of the net1-1 mutant allele induce autophagy in normal conditions [42].…”

“…Therefore, the research accumulated over recent years demonstrates that besides mitotic progression, and more specifically the regulation of mitotic exit, many other fundamental processes are also under the control of proteins from the Cdc14 family, from yeast to metazoans. In this review, we aim to summarize and disclose all these novel aspects of Cdc14 regulation and functions ( Figure 1), which include from centrosome duplication [12,27,28] to DNA repair [29][30][31]; chromosome compaction, segregation, or transcription [32][33][34][35][36]; cytokinesis [37,38]; morphogenesis [39][40][41]; and autophagy [42], among others.…”

“…Excitingly, Cdc14 also works as a central hub that coordinates mitotic progression with signaling pathways such as high-osmolarity glycerol (HOG) or target of rapamycin complex 1 (TORC1) [54][55][56]. Notably, however, Cdc14 functions are not restricted to cell cycle regulation, as the phosphatase can also induce autophagy under starvation stress [42].…”