PP2A Cdc55 Phosphatase Imposes Ordered Cell-Cycle Phosphorylation by Opposing Threonine Phosphorylation
Abstract
In the quantitative model of cell-cycle control, progression from G1 through S phase and into mitosis is ordered by thresholds of increasing cyclin-dependent kinase (Cdk) activity. How such thresholds are read out by substrates that respond with the correct phosphorylation timing is not known. Here, using the budding yeast model, we show that the abundant PP2A Cdc55 phosphatase counteracts Cdk phosphorylation during interphase and delays phosphorylation of late Cdk substrates. PP2A Cdc55 specifically counteracts phosphorylation on threonine residues, and consequently, we find that threonine-directed phosphorylation occurs late in the cell cycle. Furthermore, the late phosphorylation of a model substrate, Ndd1, depends on threonine identity of its Cdk target sites. Our results support a model in which Cdk-counteracting phosphatases contribute to cell-cycle ordering by imposing Cdk thresholds. They also unveil a regulatory principle based on the phosphoacceptor amino acid, which is likely to apply to signaling pathways beyond cell-cycle control.
Related
- Serine-threonine kinase 38 exerts a cancer-promoting role in hepatocellular carcinoma by stabilizing the Notch intracellular domain
- P019 Below the lower limit - trending lifelong alkaline phosphatase leading to a diagnosis of adult hypophosphatasia
- Disrupting the Kinase–Phosphatase Equilibrium: A Unified Mechanism for Drug-Induced Eryptosis
- Effects of Tricine, Glycine and Tris Buffers on Alkaline Phosphatase Activity
- P015 Long-standing isolated alkaline phosphatase elevation attributed to vitamin D deficiency revealing extensive polyostotic Paget’s disease of bone: a diagnostic challenge and therapeutic dilemma
BibTeX
@article{godfrey2026pp2a,
title = {{PP2A Cdc55 Phosphatase Imposes Ordered Cell-Cycle Phosphorylation by Opposing Threonine Phosphorylation}},
author = {Molly Godfrey and Sandra Touati and Meghna Kataria and Andrew Jones and Ambrosius Snijders and Frank Uhlmann},
journal = {Molecular Cell},
year = {2026},
month = sep,
doi = {10.1016/j.molcel.2016.12.018},
url = {https://hal.science/hal-05750283v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - PP2A Cdc55 Phosphatase Imposes Ordered Cell-Cycle Phosphorylation by Opposing Threonine Phosphorylation
AU - Molly Godfrey
AU - Sandra Touati
AU - Meghna Kataria
AU - Andrew Jones
AU - Ambrosius Snijders
AU - Frank Uhlmann
PY - 2026
DA - 2026/09/15
JO - Molecular Cell
DO - 10.1016/j.molcel.2016.12.018
UR - https://hal.science/hal-05750283v1
AB - In the quantitative model of cell-cycle control, progression from G1 through S phase and into mitosis is ordered by thresholds of increasing cyclin-dependent kinase (Cdk) activity. How such thresholds are read out by substrates that respond with the correct phosphorylation timing is not known. Here, using the budding yeast model, we show that the abundant PP2A Cdc55 phosphatase counteracts Cdk phosphorylation during interphase and delays phosphorylation of late Cdk substrates. PP2A Cdc55 specifically counteracts phosphorylation on threonine residues, and consequently, we find that threonine-directed phosphorylation occurs late in the cell cycle. Furthermore, the late phosphorylation of a model substrate, Ndd1, depends on threonine identity of its Cdk target sites. Our results support a model in which Cdk-counteracting phosphatases contribute to cell-cycle ordering by imposing Cdk thresholds. They also unveil a regulatory principle based on the phosphoacceptor amino acid, which is likely to apply to signaling pathways beyond cell-cycle control.
SN - 1097-2765
SN - 1097-4164
ER -