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

Temporal changes of RENT, Net1 forms and fluxes in cdc15-2 cells blocked at telophase in mitosis.Simulation was done similar to Figure 5A.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3285609&req=5

pone-0030810-g007: Temporal changes of RENT, Net1 forms and fluxes in cdc15-2 cells blocked at telophase in mitosis.Simulation was done similar to Figure 5A.

Mentions: The flux diagrams for NET1-6cdk and cdc15-2 mutant cells are shown in Figure 6 and Figure 7, respectively. Figure 7 shows that, after anaphase onset, fluxes in the path RENTPRENTPRENTP are increased because of high Cdc5. Fluxes through RENTRENTPPRENTP do not play a major role in the transient release of Cdc14 because of higher phosphatase activity in this path (as in wild-type cells). In cdc15-2 cells, Net1 gets phosphorylated first by Cdc5 and then by Cdk/Clb2 in our model, and Cdc14 gets released from PRENT and PRENTP. At telophase arrest, all variables reach their steady state values where some portion of Net1 stays in the phosphorylated form, and kinase activities are reduced to about half of their metaphase levels. Cdc14 reaches a peak value, which is less than half of its peak in wild-type cells, before it is sequestered back into RENT. RENT returns to metaphase levels, and PRENT stays a little elevated due to remaining Cdc5 activity. PNet1P and PNet1, released from PRENT and PRENTP, are dephosphorylated by Cdc14 and move back to RENT after capturing free Cdc14.


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

Hancioglu B, Tyson JJ - PLoS ONE (2012)

Temporal changes of RENT, Net1 forms and fluxes in cdc15-2 cells blocked at telophase in mitosis.Simulation was done similar to Figure 5A.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0030810-g007: Temporal changes of RENT, Net1 forms and fluxes in cdc15-2 cells blocked at telophase in mitosis.Simulation was done similar to Figure 5A.
Mentions: The flux diagrams for NET1-6cdk and cdc15-2 mutant cells are shown in Figure 6 and Figure 7, respectively. Figure 7 shows that, after anaphase onset, fluxes in the path RENTPRENTPRENTP are increased because of high Cdc5. Fluxes through RENTRENTPPRENTP do not play a major role in the transient release of Cdc14 because of higher phosphatase activity in this path (as in wild-type cells). In cdc15-2 cells, Net1 gets phosphorylated first by Cdc5 and then by Cdk/Clb2 in our model, and Cdc14 gets released from PRENT and PRENTP. At telophase arrest, all variables reach their steady state values where some portion of Net1 stays in the phosphorylated form, and kinase activities are reduced to about half of their metaphase levels. Cdc14 reaches a peak value, which is less than half of its peak in wild-type cells, before it is sequestered back into RENT. RENT returns to metaphase levels, and PRENT stays a little elevated due to remaining Cdc5 activity. PNet1P and PNet1, released from PRENT and PRENTP, are dephosphorylated by Cdc14 and move back to RENT after capturing free Cdc14.

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