Queralt2006 - Initiation of mitotic exit by downregulation of PP2A in budding yeast

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Mathematical model of mitotic exit in budding yeast.

Related Publication
  • Downregulation of PP2A(Cdc55) phosphatase by separase initiates mitotic exit in budding yeast.
  • Queralt E, Lehane C, Novak B, Uhlmann F
  • Cell , 5/ 2006 , Volume 125 , pages: 719-732 , PubMed ID: 16713564
  • Chromosome Segregation Laboratory, Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom.
  • After anaphase, the high mitotic cyclin-dependent kinase (Cdk) activity is downregulated to promote exit from mitosis. To this end, in the budding yeast S. cerevisiae, the Cdk counteracting phosphatase Cdc14 is activated. In metaphase, Cdc14 is kept inactive in the nucleolus by its inhibitor Net1. During anaphase, Cdk- and Polo-dependent phosphorylation of Net1 is thought to release active Cdc14. How Net1 is phosphorylated specifically in anaphase, when mitotic kinase activity starts to decline, has remained unexplained. Here, we show that PP2A(Cdc55) phosphatase keeps Net1 underphosphorylated in metaphase. The sister chromatid-separating protease separase, activated at anaphase onset, interacts with and downregulates PP2A(Cdc55), thereby facilitating Cdk-dependent Net1 phosphorylation. PP2A(Cdc55) downregulation also promotes phosphorylation of Bfa1, contributing to activation of the "mitotic exit network" that sustains Cdc14 as Cdk activity declines. These findings allow us to present a new quantitative model for mitotic exit in budding yeast.
Submitter of the first revision: Matthieu MAIRE
Submitter of this revision: Krishna Kumar Tiwari
Modellers: Matthieu MAIRE, Krishna Kumar Tiwari

Metadata information

is (2 statements)
BioModels Database BIOMD0000000953
BioModels Database MODEL1809060004

isDescribedBy (2 statements)
hasTaxon (1 statement)
isVersionOf (1 statement)
hasProperty (1 statement)
Mathematical Modelling Ontology Ordinary differential equation model

unknownQualifier (1 statement)
Mathematical Modelling Ontology Ordinary differential equation model

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Model files

queralt2006_final.xml SBML L2V4 representation of Queralt2006 - Initiation of mitotic exit by downregulation of PP2A in budding yeast 157.41 KB Preview | Download

Additional files

queralt2006_final.cps Copasi file (version 4.23 Build 184) for reproducing figure 7B in the reference publication. 215.33 KB Preview | Download
queralt2006_final.sedml SEDML file for reproducing figure 7B in the reference publication. 5.97 KB Preview | Download

  • Model originally submitted by : Matthieu MAIRE
  • Submitted: Sep 6, 2018 1:39:56 PM
  • Last Modified: May 18, 2020 12:22:02 PM
  • Version: 4 public model Download this version
    • Submitted on: May 18, 2020 12:22:02 PM
    • Submitted by: Krishna Kumar Tiwari
    • With comment: Automatically added model identifier BIOMD0000000953
  • Version: 2 public model Download this version
    • Submitted on: Sep 6, 2018 1:39:56 PM
    • Submitted by: Matthieu MAIRE
    • With comment: Edited model metadata online.

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: Variable used inside SBML models

Species Initial Concentration/Amount

Nucleolar protein NET1
0.098 mmol

Cell division control protein 15
0.0257 mmol

0.352 mmol
securin separase

Securin ; Separin ; protein complex
0.248 mmol

Cyclin-dependent kinase 1
0.997 mmol

Cell cycle serine/threonine-protein kinase CDC5/MSD2
0.945 mmol
men 8.0E-6 mmol

G2/mitotic-specific cyclin-2
0.997 mmol
Reactions Rate Parameters
net1 => ; cdk, men, net1cdc14 nucleus*(kp*cdk+kp_p*men)*net1/(Jnet+net1+net1cdc14) kp = 0.4; kp_p = 2.0; Jnet = 0.2
=> cdc15; cdc14, cdc15_total nucleus*(ka_cdc15+ka_cdc15_p*cdc14)*(cdc15_total-cdc15)/((J_cdc15+cdc15_total)-cdc15) ka_cdc15_p = 0.5; ka_cdc15 = 0.02; J_cdc15 = 0.2
securin = securin_total-securin_separase [] []
securin_separase => ; cdc20 nucleus*(ld_securin+kd_separase+kd_securin+kd_securin_p*cdc20)*securin_separase kd_separase = 0.004; ld_securin = 1.0; kd_securin = 0.05; kd_securin_p = 2.0
=> net1; cdc14, pp2a, net1p nucleus*(kd_p*cdc14+kd*pp2a)*net1p/(Jnet+net1p) kd = 0.45; Jnet = 0.2; kd_p = 0.1
cdk = clb2/(1+Inh) [] []
polo => nucleus*ki_polo*polo/(J_polo+polo) J_polo = 0.25; ki_polo = 0.1
=> men; tem1, cdc15 nucleus*la_men*(tem1-men)*(cdc15-men) la_men = 10.0
men => nucleus*ld_men*men ld_men = 0.01
=> clb2 nucleus*ks_clb2 ks_clb2 = 0.03
Curator's comment:
(added: 06 Sep 2018, 14:00:16, updated: 06 Sep 2018, 14:00:16)
Figure 7B (bottom) of the reference publication has been reproduced using Copasi 4.23 (Build 184). Use attached SEDML file to reproduce figure 7B.