Limits...
A mathematical model of mitotic exit in budding yeast: the role of Polo kinase.

Hancioglu B, Tyson JJ - PLoS ONE (2012)

Bottom Line: Entry into mitosis requires phosphorylation of many proteins targeted by mitotic Cdk, and exit from mitosis requires proteolysis of mitotic cyclins and dephosphorylation of their targeted proteins.The model captures the dynamics of this network in wild-type yeast cells and 110 mutant strains.The model clarifies the roles of Polo-like kinase (Cdc5) in the Cdc14 early anaphase release pathway and in the G-protein regulated mitotic exit network.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, United States of America. barish@rice.edu

ABSTRACT
Cell cycle progression in eukaryotes is regulated by periodic activation and inactivation of a family of cyclin-dependent kinases (Cdk's). Entry into mitosis requires phosphorylation of many proteins targeted by mitotic Cdk, and exit from mitosis requires proteolysis of mitotic cyclins and dephosphorylation of their targeted proteins. Mitotic exit in budding yeast is known to involve the interplay of mitotic kinases (Cdk and Polo kinases) and phosphatases (Cdc55/PP2A and Cdc14), as well as the action of the anaphase promoting complex (APC) in degrading specific proteins in anaphase and telophase. To understand the intricacies of this mechanism, we propose a mathematical model for the molecular events during mitotic exit in budding yeast. The model captures the dynamics of this network in wild-type yeast cells and 110 mutant strains. The model clarifies the roles of Polo-like kinase (Cdc5) in the Cdc14 early anaphase release pathway and in the G-protein regulated mitotic exit network.

Show MeSH

Related in: MedlinePlus

Flux diagrams in wild-type cells.Initially cells are in the metaphase steady state by Cdc20 deprivation. Cdc20 activation at time zero (ks,20 = 0.015) induces mitotic progression through anaphase, telophase and G1. Flux definitions are given in Table S1.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3285609&req=5

pone-0030810-g003: Flux diagrams in wild-type cells.Initially cells are in the metaphase steady state by Cdc20 deprivation. Cdc20 activation at time zero (ks,20 = 0.015) induces mitotic progression through anaphase, telophase and G1. Flux definitions are given in Table S1.

Mentions: The metaphase-arrested state is very dynamic, with rapid rates of phosphorylation and dephosphorylation of Net1, due to high activities of kinases (Cdk/Clb2 and Cdc5) and the opposing phosphatase, PP2A (Flux diagrams are presented in Figure 3). In metaphase, Cdc5 activity is high, and it continuously phosphorylates RENT to PRENT, which rapidly dissociates into Cdc14 and PNet1. At the same time, high activity of Cdk/Clb2 phosphorylates Net1 subunits to PRENTP, which also dissociates rapidly to Cdc14 and PNet1P. Nonetheless, PP2A activity is also high in metaphase, and this phosphatase converts PNet1 and PNet1P to Net1. Under these conditions, there is an excess of Net1, which avidly captures free Cdc14, sequestering it back into RENT. The dynamic balance among these fluxes in metaphase (Figure 3) maintains high steady state levels of Net1 and RENT, and low levels of the phosphorylated forms of these proteins.


A mathematical model of mitotic exit in budding yeast: the role of Polo kinase.

Hancioglu B, Tyson JJ - PLoS ONE (2012)

Flux diagrams in wild-type cells.Initially cells are in the metaphase steady state by Cdc20 deprivation. Cdc20 activation at time zero (ks,20 = 0.015) induces mitotic progression through anaphase, telophase and G1. Flux definitions are given in Table S1.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3285609&req=5

pone-0030810-g003: Flux diagrams in wild-type cells.Initially cells are in the metaphase steady state by Cdc20 deprivation. Cdc20 activation at time zero (ks,20 = 0.015) induces mitotic progression through anaphase, telophase and G1. Flux definitions are given in Table S1.
Mentions: The metaphase-arrested state is very dynamic, with rapid rates of phosphorylation and dephosphorylation of Net1, due to high activities of kinases (Cdk/Clb2 and Cdc5) and the opposing phosphatase, PP2A (Flux diagrams are presented in Figure 3). In metaphase, Cdc5 activity is high, and it continuously phosphorylates RENT to PRENT, which rapidly dissociates into Cdc14 and PNet1. At the same time, high activity of Cdk/Clb2 phosphorylates Net1 subunits to PRENTP, which also dissociates rapidly to Cdc14 and PNet1P. Nonetheless, PP2A activity is also high in metaphase, and this phosphatase converts PNet1 and PNet1P to Net1. Under these conditions, there is an excess of Net1, which avidly captures free Cdc14, sequestering it back into RENT. The dynamic balance among these fluxes in metaphase (Figure 3) maintains high steady state levels of Net1 and RENT, and low levels of the phosphorylated forms of these proteins.

Bottom Line: Entry into mitosis requires phosphorylation of many proteins targeted by mitotic Cdk, and exit from mitosis requires proteolysis of mitotic cyclins and dephosphorylation of their targeted proteins.The model captures the dynamics of this network in wild-type yeast cells and 110 mutant strains.The model clarifies the roles of Polo-like kinase (Cdc5) in the Cdc14 early anaphase release pathway and in the G-protein regulated mitotic exit network.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, United States of America. barish@rice.edu

ABSTRACT
Cell cycle progression in eukaryotes is regulated by periodic activation and inactivation of a family of cyclin-dependent kinases (Cdk's). Entry into mitosis requires phosphorylation of many proteins targeted by mitotic Cdk, and exit from mitosis requires proteolysis of mitotic cyclins and dephosphorylation of their targeted proteins. Mitotic exit in budding yeast is known to involve the interplay of mitotic kinases (Cdk and Polo kinases) and phosphatases (Cdc55/PP2A and Cdc14), as well as the action of the anaphase promoting complex (APC) in degrading specific proteins in anaphase and telophase. To understand the intricacies of this mechanism, we propose a mathematical model for the molecular events during mitotic exit in budding yeast. The model captures the dynamics of this network in wild-type yeast cells and 110 mutant strains. The model clarifies the roles of Polo-like kinase (Cdc5) in the Cdc14 early anaphase release pathway and in the G-protein regulated mitotic exit network.

Show MeSH
Related in: MedlinePlus