The regulation of Net1/Cdc14 by the Hog1 MAPK upon osmostress unravels a new mechanism regulating mitosis

Jiménez, Javier; Queralt, Ethel; Posas, Francesc; Nadal, Eulàlia de

doi:10.1080/15384101.2020.1804222

Cited by 10 publications

(4 citation statements)

References 163 publications

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“…For full adaption to extracellular stimuli, Hog1 exerts several adaptive responses in the cell, including the regulation of cell cycle progression [ 44 , 45 ]. Consequently, we analyzed whether Hog1 was important in the mediation of cell-cycle delay upon copper exposure.…”

Section: Resultsmentioning

confidence: 99%

Involvement of the High-Osmolarity Glycerol Pathway of Saccharomyces Cerevisiae in Protection against Copper Toxicity

Ren

Han

et al. 2022

Antioxidants

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Although essential for life, copper is also potentially toxic in concentrations that surpass physiological thresholds. The high-osmolarity glycerol pathway of yeast is the main regulator of adaptive responses and is known to play crucial roles in the responses to various stressors. The objective of this research is to determine whether the HOG pathway could be activated and to investigate the possible interplay of the HOG pathway and oxidative stress due to copper exposure. In this research, we demonstrate that copper could induce oxidative stress, including the elevated concentrations of reactive oxygen species (ROS) and malondialdehyde (MDA). Increased combination with GSH, increased intracellular SOD activity, and the up-regulation of relevant genes can help cells defend themselves against oxidative toxicity. The results show that copper treatment triggers marked and prolonged Hog1 phosphorylation. Significantly, oxidative stress generated by copper toxicity is essential for the activation of Hog1. Activated Hog1 is translocated to the nucleus to regulate the expressions of genes such as CTT1, GPD1, and HSP12, among others. Furthermore, copper exposure induced significant G1-phase cell cycle arrest, while Hog1 partially participated in the regulation of cell cycle progression. These novel findings reveal another role for Hog1 in the regulation of copper-induced cellular stress.

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Section: Resultsmentioning

confidence: 99%

Involvement of the High-Osmolarity Glycerol Pathway of Saccharomyces Cerevisiae in Protection against Copper Toxicity

Ren

Han

et al. 2022

Antioxidants

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“…Just as Hog1 modulates physiology via multiple mechanisms in response to stress, it also initiates cell cycle arrest by several methods: First, Hog1 delays the expression of cell phase-specific transcripts to prevent progression. Second, Hog1 directly phosphorylates cell cycle regulatory proteins to modulate their activity, thus preventing progression [ 231 , 232 , 233 , 234 , 235 , 236 , 237 , 238 , 239 , 240 ]. Thus, proper Hog1 activity to promote cell cycle arrest in response to stress is crucial for cell survival.…”

Section: Key Regulators That Govern Physiological Pathways Rewired Fo...mentioning

confidence: 99%

Advances in S. cerevisiae Engineering for Xylose Fermentation and Biofuel Production: Balancing Growth, Metabolism, and Defense

Wagner

Gasch

2023

JoF

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Genetically engineering microorganisms to produce chemicals has changed the industrialized world. The budding yeast Saccharomyces cerevisiae is frequently used in industry due to its genetic tractability and unique metabolic capabilities. S. cerevisiae has been engineered to produce novel compounds from diverse sugars found in lignocellulosic biomass, including pentose sugars, like xylose, not recognized by the organism. Engineering high flux toward novel compounds has proved to be more challenging than anticipated since simply introducing pathway components is often not enough. Several studies show that the rewiring of upstream signaling is required to direct products toward pathways of interest, but doing so can diminish stress tolerance, which is important in industrial conditions. As an example of these challenges, we reviewed S. cerevisiae engineering efforts, enabling anaerobic xylose fermentation as a model system and showcasing the regulatory interplay’s controlling growth, metabolism, and stress defense. Enabling xylose fermentation in S. cerevisiae requires the introduction of several key metabolic enzymes but also regulatory rewiring of three signaling pathways at the intersection of the growth and stress defense responses: the RAS/PKA, Snf1, and high osmolarity glycerol (HOG) pathways. The current studies reviewed here suggest the modulation of global signaling pathways should be adopted into biorefinery microbial engineering pipelines to increase efficient product yields.

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“…It was recently shown that activated Hog1 phosphorylates the core subunit of the RENT complex, Net1, at Thr62 and Ser385, and in that way alters its affinity for the dual-specificity phosphatase Cdc14 (Jimenez et al . 2020 ). The activity of Cdc14 is tightly regulated by its subcellular localization, and during most of the cell cycle Cdc14 is kept sequestered at the nucleolus by Net1.…”

Section: The Cell Cycle and Osmostressmentioning

confidence: 99%

“…The Hog1-dependent phosphorylation of Net1 makes the Net1-Cdc14 complex more resistant to modifications by CDK and leads to that Cdc14 is sequestered at the nucleolus and mitosis is delayed (Jimenez et al . 2020 ). Consequently, the phosphorylation-negative mutant of Net1 (Thr62Ala, Ser385Ala), that cannot be phosphorylated by Hog1, displays reduced viability upon osmostress.…”

Section: The Cell Cycle and Osmostressmentioning

confidence: 99%

Yeast osmoregulation – glycerol still in pole position

Blomberg

2022

FEMS Yeast Research

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In response to osmotic dehydration cells sense, signal, alter gene expression and metabolically counterbalance osmotic differences. The main compatible solute/osmolyte that accumulates in yeast cells is glycerol, which is produced from the glycolytic intermediate dihydroxyacetone phosphate. This review covers recent advancements in understanding mechanisms involved in sensing, signaling, cell-cycle delays, transcriptional responses as well as post-translational modifications on key proteins in osmoregulation. The protein kinase Hog1 is a key-player in many of these events, however, there is also a growing body of evidence for important Hog1-independent mechanisms playing vital roles. Several missing links in our understanding of osmoregulation will be discussed and future avenues for research proposed. The review highlights that this rather simple experimental system—salt/sorbitol and yeast—has developed into an enormously potent model system unravelling important fundamental aspects in biology. ‘Striving for an integrative view’ (Stefan Hohmann, 2002)

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The regulation of Net1/Cdc14 by the Hog1 MAPK upon osmostress unravels a new mechanism regulating mitosis

Cited by 10 publications

References 163 publications

Involvement of the High-Osmolarity Glycerol Pathway of Saccharomyces Cerevisiae in Protection against Copper Toxicity

Involvement of the High-Osmolarity Glycerol Pathway of Saccharomyces Cerevisiae in Protection against Copper Toxicity

Advances in S. cerevisiae Engineering for Xylose Fermentation and Biofuel Production: Balancing Growth, Metabolism, and Defense

Yeast osmoregulation – glycerol still in pole position

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