Coupling TOR to the Cell Cycle by the Greatwall–Endosulfine–PP2A-B55 Pathway

Cell growth and division are two processes tightly coupled in proliferating cells. While Target of Rapamycin (TOR) is the master regulator of growth, the cell cycle is dictated by the activity of the cyclin-dependent kinases (CDKs). A long-standing question in cell biology is how these processes may...

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Main Authors: Livia Pérez-Hidalgo, Sergio Moreno
Format: Article
Language:English
Published: MDPI AG 2017-08-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/7/3/59
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author Livia Pérez-Hidalgo
Sergio Moreno
author_facet Livia Pérez-Hidalgo
Sergio Moreno
author_sort Livia Pérez-Hidalgo
collection DOAJ
description Cell growth and division are two processes tightly coupled in proliferating cells. While Target of Rapamycin (TOR) is the master regulator of growth, the cell cycle is dictated by the activity of the cyclin-dependent kinases (CDKs). A long-standing question in cell biology is how these processes may be connected. Recent work has highlighted that regulating the phosphatases that revert CDK phosphorylations is as important as regulating the CDKs for cell cycle progression. At mitosis, maintaining a low level of protein phosphatase 2A (PP2A)-B55 activity is essential for CDK substrates to achieve the correct level of phosphorylation. The conserved Greatwall–Endosulfine pathway has been shown to be required for PP2A-B55 inhibition at mitosis in yeasts and multicellular organisms. Interestingly, in yeasts, the Greatwall–Endosulfine pathway is negatively regulated by TOR Complex 1 (TORC1). Moreover, Greatwall–Endosulfine activation upon TORC1 inhibition has been shown to regulate the progression of the cell cycle at different points: the G1 phase in budding yeast, the G2/M transition and the differentiation response in fission yeast, and the entry into quiescence in both budding and fission yeasts. In this review, we discuss the recent findings on how the Greatwall–Endosulfine pathway may provide a connection between cell growth and the cell cycle machinery.
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spelling doaj.art-093683e107c84b29b6fb46b8769e35d32022-12-21T17:16:33ZengMDPI AGBiomolecules2218-273X2017-08-01735910.3390/biom7030059biom7030059Coupling TOR to the Cell Cycle by the Greatwall–Endosulfine–PP2A-B55 PathwayLivia Pérez-Hidalgo0Sergio Moreno1Institute of Functional Biology and Genomics (IBFG), CSIC/University of Salamanca, 37007 Salamanca, SpainInstitute of Functional Biology and Genomics (IBFG), CSIC/University of Salamanca, 37007 Salamanca, SpainCell growth and division are two processes tightly coupled in proliferating cells. While Target of Rapamycin (TOR) is the master regulator of growth, the cell cycle is dictated by the activity of the cyclin-dependent kinases (CDKs). A long-standing question in cell biology is how these processes may be connected. Recent work has highlighted that regulating the phosphatases that revert CDK phosphorylations is as important as regulating the CDKs for cell cycle progression. At mitosis, maintaining a low level of protein phosphatase 2A (PP2A)-B55 activity is essential for CDK substrates to achieve the correct level of phosphorylation. The conserved Greatwall–Endosulfine pathway has been shown to be required for PP2A-B55 inhibition at mitosis in yeasts and multicellular organisms. Interestingly, in yeasts, the Greatwall–Endosulfine pathway is negatively regulated by TOR Complex 1 (TORC1). Moreover, Greatwall–Endosulfine activation upon TORC1 inhibition has been shown to regulate the progression of the cell cycle at different points: the G1 phase in budding yeast, the G2/M transition and the differentiation response in fission yeast, and the entry into quiescence in both budding and fission yeasts. In this review, we discuss the recent findings on how the Greatwall–Endosulfine pathway may provide a connection between cell growth and the cell cycle machinery.https://www.mdpi.com/2218-273X/7/3/59cell growthcell cycleTORGreatwallEndosulfinePP2A-B55
spellingShingle Livia Pérez-Hidalgo
Sergio Moreno
Coupling TOR to the Cell Cycle by the Greatwall–Endosulfine–PP2A-B55 Pathway
Biomolecules
cell growth
cell cycle
TOR
Greatwall
Endosulfine
PP2A-B55
title Coupling TOR to the Cell Cycle by the Greatwall–Endosulfine–PP2A-B55 Pathway
title_full Coupling TOR to the Cell Cycle by the Greatwall–Endosulfine–PP2A-B55 Pathway
title_fullStr Coupling TOR to the Cell Cycle by the Greatwall–Endosulfine–PP2A-B55 Pathway
title_full_unstemmed Coupling TOR to the Cell Cycle by the Greatwall–Endosulfine–PP2A-B55 Pathway
title_short Coupling TOR to the Cell Cycle by the Greatwall–Endosulfine–PP2A-B55 Pathway
title_sort coupling tor to the cell cycle by the greatwall endosulfine pp2a b55 pathway
topic cell growth
cell cycle
TOR
Greatwall
Endosulfine
PP2A-B55
url https://www.mdpi.com/2218-273X/7/3/59
work_keys_str_mv AT liviaperezhidalgo couplingtortothecellcyclebythegreatwallendosulfinepp2ab55pathway
AT sergiomoreno couplingtortothecellcyclebythegreatwallendosulfinepp2ab55pathway