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Protein Phosphatases and Cell Cycle Regulation in Yeasts
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Protein Phosphatases and Cell Cycle Regulation in Yeasts

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: closed (5 November 2019) | Viewed by 31619

Special Issue Editors

Prof. Dr. Joaquin Arino

E-Mail Website
Guest Editor
Department of Biochemistry & Molecular Biology and Institute of Biotechnology & Biomedicine, Universitat Autònoma de Barcelona, Cerdanyola del Vallès 08193, Barcelona, Spain
Interests: yeast molecular biology; protein phosphorylation; protein phosphatases; signal transduction; cation homeostasis; cell cycle; gene expression; transcriptomics
Special Issues, Collections and Topics in MDPI journals
Dr. Ethel Queralt

E-Mail Website
Guest Editor
Cell Cycle Group, Cancer Epigenetics and Biology Program, Institut d’Investigacions Biomedica de Bellvitge (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain

Special Issue Information

Dear Colleagues,

Control of progression along the cell cycle is a key process in living cells. Such regulation is largely based on protein phospho-dephosphorylation events, catalyzed by protein kinases (PK) and phosphatases (PPases), respectively. Soon after their discovery, Cdks, the highly conserved and specific family of cyclin-dependent serine/threonine kinases, were considered the main component of the cell cycle control system. Only recently has the importance of the regulatory contribution of the opposing PPases emerged. Research on yeast has provided many insights into such contributions. Here we present an overview of the regulatory network that controls the progression across the different steps of the cell cycle in yeasts, with a particular emphasis on the role played by PPases.

Prof. Joaquin Arino
Dr. Ethel Queralt
Guest Editors

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Keywords

  • cell cycle
  • mitosis
  • meiosis
  • checkpoint
  • Ser/Thr protein phosphatases
  • dual phosphatases
  • yeasts
  • spindle dynamics
  • DNA replication and repair in personalized medicine

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Published Papers (6 papers)

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Review

15 pages, 517 KiB  
Review
The Multiple Roles of the Cdc14 Phosphatase in Cell Cycle Control
by Javier Manzano-López and Fernando Monje-Casas
Int. J. Mol. Sci. 2020, 21(3), 709; https://doi.org/10.3390/ijms21030709 - 21 Jan 2020
Cited by 19 | Viewed by 5533
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Protein Phosphatases and Cell Cycle Regulation in Yeasts)
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26 pages, 915 KiB  
Review
Cell Cycle and DNA Repair Regulation in the Damage Response: Protein Phosphatases Take Over the Reins
by Adrián Campos and Andrés Clemente-Blanco
Int. J. Mol. Sci. 2020, 21(2), 446; https://doi.org/10.3390/ijms21020446 - 10 Jan 2020
Cited by 60 | Viewed by 8263
Abstract
Cells are constantly suffering genotoxic stresses that affect the integrity of our genetic material. Genotoxic insults must be repaired to avoid the loss or inappropriate transmission of the genetic information, a situation that could lead to the appearance of developmental abnormalities and tumorigenesis. [...] Read more.
Cells are constantly suffering genotoxic stresses that affect the integrity of our genetic material. Genotoxic insults must be repaired to avoid the loss or inappropriate transmission of the genetic information, a situation that could lead to the appearance of developmental abnormalities and tumorigenesis. To combat this threat, eukaryotic cells have evolved a set of sophisticated molecular mechanisms that are collectively known as the DNA damage response (DDR). This surveillance system controls several aspects of the cellular response, including the detection of lesions, a temporary cell cycle arrest, and the repair of the broken DNA. While the regulation of the DDR by numerous kinases has been well documented over the last decade, the complex roles of protein dephosphorylation have only recently begun to be investigated. Here, we review recent progress in the characterization of DDR-related protein phosphatases during the response to a DNA lesion, focusing mainly on their ability to modulate the DNA damage checkpoint and the repair of the damaged DNA. We also discuss their protein composition and structure, target specificity, and biochemical regulation along the different stages encompassed in the DDR. The compilation of this information will allow us to better comprehend the physiological significance of protein dephosphorylation in the maintenance of genome integrity and cell viability in response to genotoxic stress. Full article
(This article belongs to the Special Issue Protein Phosphatases and Cell Cycle Regulation in Yeasts)
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15 pages, 2771 KiB  
Review
Protein Phosphatases in G1 Regulation
by Ruth Martín, Vilte Stonyte and Sandra Lopez-Aviles
Int. J. Mol. Sci. 2020, 21(2), 395; https://doi.org/10.3390/ijms21020395 - 8 Jan 2020
Cited by 9 | Viewed by 4114
Abstract
Eukaryotic cells make the decision to proliferate, to differentiate or to cease dividing during G1, before passage through the restriction point or Start. Keeping cyclin-dependent kinase (CDK) activity low during this period restricts commitment to a new cell cycle and is essential to [...] Read more.
Eukaryotic cells make the decision to proliferate, to differentiate or to cease dividing during G1, before passage through the restriction point or Start. Keeping cyclin-dependent kinase (CDK) activity low during this period restricts commitment to a new cell cycle and is essential to provide the adequate timeframe for the sensing of environmental signals. Here, we review the role of protein phosphatases in the modulation of CDK activity and as the counteracting force for CDK-dependent substrate phosphorylation, in budding and fission yeast. Moreover, we discuss recent findings that place protein phosphatases in the interface between nutritional signalling pathways and the cell cycle machinery. Full article
(This article belongs to the Special Issue Protein Phosphatases and Cell Cycle Regulation in Yeasts)
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13 pages, 2166 KiB  
Review
PP2A Functions during Mitosis and Cytokinesis in Yeasts
by Yolanda Moyano-Rodriguez and Ethel Queralt
Int. J. Mol. Sci. 2020, 21(1), 264; https://doi.org/10.3390/ijms21010264 - 30 Dec 2019
Cited by 8 | Viewed by 4307
Abstract
Protein phosphorylation is a common mechanism for the regulation of cell cycle progression. The opposing functions of cell cycle kinases and phosphatases are crucial for accurate chromosome segregation and exit from mitosis. Protein phosphatases 2A are heterotrimeric complexes that play essential roles in [...] Read more.
Protein phosphorylation is a common mechanism for the regulation of cell cycle progression. The opposing functions of cell cycle kinases and phosphatases are crucial for accurate chromosome segregation and exit from mitosis. Protein phosphatases 2A are heterotrimeric complexes that play essential roles in cell growth, proliferation, and regulation of the cell cycle. Here, we review the function of the protein phosphatase 2A family as the counteracting force for the mitotic kinases. We focus on recent findings in the regulation of mitotic exit and cytokinesis by PP2A phosphatases in S. cerevisiae and other fungal species. Full article
(This article belongs to the Special Issue Protein Phosphatases and Cell Cycle Regulation in Yeasts)
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15 pages, 1925 KiB  
Review
Greatwall-Endosulfine: A Molecular Switch that Regulates PP2A/B55 Protein Phosphatase Activity in Dividing and Quiescent Cells
by Natalia García-Blanco, Alicia Vázquez-Bolado and Sergio Moreno
Int. J. Mol. Sci. 2019, 20(24), 6228; https://doi.org/10.3390/ijms20246228 - 10 Dec 2019
Cited by 11 | Viewed by 4860
Abstract
During the cell cycle, hundreds of proteins become phosphorylated and dephosphorylated, indicating that protein kinases and protein phosphatases play a central role in its regulation. It has been widely recognized that oscillation in cyclin-dependent kinase (CDK) activity promotes DNA replication, during S-phase, and [...] Read more.
During the cell cycle, hundreds of proteins become phosphorylated and dephosphorylated, indicating that protein kinases and protein phosphatases play a central role in its regulation. It has been widely recognized that oscillation in cyclin-dependent kinase (CDK) activity promotes DNA replication, during S-phase, and chromosome segregation, during mitosis. Each CDK substrate phosphorylation status is defined by the balance between CDKs and CDK-counteracting phosphatases. In fission yeast and animal cells, PP2A/B55 is the main protein phosphatase that counteracts CDK activity. PP2A/B55 plays a key role in mitotic entry and mitotic exit, and it is regulated by the Greatwall-Endosulfine (ENSA) molecular switch that inactivates PP2A/B55 at the onset of mitosis, allowing maximal CDK activity at metaphase. The Greatwall-ENSA-PP2A/B55 pathway is highly conserved from yeast to animal cells. In yeasts, Greatwall is negatively regulated by nutrients through TORC1 and S6 kinase, and couples cell growth, regulated by TORC1, to cell cycle progression, driven by CDK activity. In animal cells, Greatwall is phosphorylated and activated by Cdk1 at G2/M, generating a bistable molecular switch that results in full activation of Cdk1/CyclinB. Here we review the current knowledge of the Greatwall-ENSA-PP2A/B55 pathway and discuss its role in cell cycle progression and as an integrator of nutritional cues. Full article
(This article belongs to the Special Issue Protein Phosphatases and Cell Cycle Regulation in Yeasts)
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17 pages, 2431 KiB  
Review
The Opposing Functions of Protein Kinases and Phosphatases in Chromosome Bipolar Attachment
by Delaney Sherwin and Yanchang Wang
Int. J. Mol. Sci. 2019, 20(24), 6182; https://doi.org/10.3390/ijms20246182 - 7 Dec 2019
Cited by 8 | Viewed by 4049
Abstract
Accurate chromosome segregation during cell division is essential to maintain genome integrity in all eukaryotic cells, and chromosome missegregation leads to aneuploidy and therefore represents a hallmark of many cancers. Accurate segregation requires sister kinetochores to attach to microtubules emanating from opposite spindle [...] Read more.
Accurate chromosome segregation during cell division is essential to maintain genome integrity in all eukaryotic cells, and chromosome missegregation leads to aneuploidy and therefore represents a hallmark of many cancers. Accurate segregation requires sister kinetochores to attach to microtubules emanating from opposite spindle poles, known as bipolar attachment or biorientation. Recent studies have uncovered several mechanisms critical to chromosome bipolar attachment. First, a mechanism exists to ensure that the conformation of sister centromeres is biased toward bipolar attachment. Second, the phosphorylation of some kinetochore proteins destabilizes kinetochore attachment to facilitate error correction, but a protein phosphatase reverses this phosphorylation. Moreover, the activity of the spindle assembly checkpoint is regulated by kinases and phosphatases at the kinetochore, and this checkpoint prevents anaphase entry in response to faulty kinetochore attachment. The fine-tuned kinase/phosphatase balance at kinetochores is crucial for faithful chromosome segregation during both mitosis and meiosis. Here, we discuss the function and regulation of protein phosphatases in the establishment of chromosome bipolar attachment with a focus on the model organism budding yeast. Full article
(This article belongs to the Special Issue Protein Phosphatases and Cell Cycle Regulation in Yeasts)
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