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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.

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Model predicts that Cdc14 is responsible for its own re-sequestration after ME.(A–C) All simulations were done similar to cdc15-2 mutant simulations in Figure 5A except that after 20 min either Cdc14 (in A, effc14 = 0) or PP2A (in B, effppa = 0) or both (in C, effc14 = effppa = 0)) were inactivated by setting their corresponding activity factors to zero.
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pone-0030810-g008: Model predicts that Cdc14 is responsible for its own re-sequestration after ME.(A–C) All simulations were done similar to cdc15-2 mutant simulations in Figure 5A except that after 20 min either Cdc14 (in A, effc14 = 0) or PP2A (in B, effppa = 0) or both (in C, effc14 = effppa = 0)) were inactivated by setting their corresponding activity factors to zero.

Mentions: The model predicts that, after Cdc14 transient release in cdc15-2 cells, inhibition of Cdc14 phosphatase activity results in an elevated level of Cdc14 protein released in telophase (Figure 8A); however, inhibition of PP2A activity has no such effect on Cdc14 release (Figure 8B). When both Cdc14 and PP2A phosphatase activities are inhibited the effect is similar to the inhibition of Cdc14 (Figure 8C). Therefore, in our model Cdc14 itself is responsible for its own re-sequestration after its transient release in MEN mutants. FEAR-released Cdc14 in MEN mutants cannot induce ME because the Cdc14/Clb2 ratio stays below the critical threshold to activate Cdh1.


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

Hancioglu B, Tyson JJ - PLoS ONE (2012)

Model predicts that Cdc14 is responsible for its own re-sequestration after ME.(A–C) All simulations were done similar to cdc15-2 mutant simulations in Figure 5A except that after 20 min either Cdc14 (in A, effc14 = 0) or PP2A (in B, effppa = 0) or both (in C, effc14 = effppa = 0)) were inactivated by setting their corresponding activity factors to zero.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0030810-g008: Model predicts that Cdc14 is responsible for its own re-sequestration after ME.(A–C) All simulations were done similar to cdc15-2 mutant simulations in Figure 5A except that after 20 min either Cdc14 (in A, effc14 = 0) or PP2A (in B, effppa = 0) or both (in C, effc14 = effppa = 0)) were inactivated by setting their corresponding activity factors to zero.
Mentions: The model predicts that, after Cdc14 transient release in cdc15-2 cells, inhibition of Cdc14 phosphatase activity results in an elevated level of Cdc14 protein released in telophase (Figure 8A); however, inhibition of PP2A activity has no such effect on Cdc14 release (Figure 8B). When both Cdc14 and PP2A phosphatase activities are inhibited the effect is similar to the inhibition of Cdc14 (Figure 8C). Therefore, in our model Cdc14 itself is responsible for its own re-sequestration after its transient release in MEN mutants. FEAR-released Cdc14 in MEN mutants cannot induce ME because the Cdc14/Clb2 ratio stays below the critical threshold to activate Cdh1.

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