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BIOMD0000000409 - Queralt2006_MitoticExit_Cdc55DownregulationBySeparase

 

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Reference Publication
Publication ID: 16713564
Queralt E, Lehane C, Novak B, Uhlmann F.
Downregulation of PP2A(Cdc55) phosphatase by separase initiates mitotic exit in budding yeast.
Cell 2006 May; 125(4): 719-732
Chromosome Segregation Laboratory, Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom.  [more]
Model
Original Model: JWS logo
Submitter: Lukas Endler
Submission ID: MODEL5951818256
Submission Date: 25 Jun 2009 18:43:40 UTC
Last Modification Date: 16 Jul 2012 12:01:33 UTC
Creation Date: 20 Aug 2009 16:15:09 UTC
Encoders:  Lukas Endler
   Vijayalakshmi Chelliah
set #1
bqbiol:isVersionOf Gene Ontology mitotic cell cycle
Cell Cycle Ontology mitotic cell cycle
set #2
bqbiol:occursIn Taxonomy Saccharomyces cerevisiae
Notes

This model is from the article:
Downregulation of PP2A(Cdc55) phosphatase by separase initiates mitotic exit in budding yeast.
Queralt E, Lehane C, Novak B, Uhlmann F. Cell. 2006 May 19;125(4):719-32. 16713564 ,
Abstract:
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.

This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2012 The BioModels.net Team.
For more information see the terms of use .
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

Model
Publication ID: 16713564 Submission Date: 25 Jun 2009 18:43:40 UTC Last Modification Date: 16 Jul 2012 12:01:33 UTC Creation Date: 20 Aug 2009 16:15:09 UTC
Mathematical expressions
Reactions
v1 v2 v3 v4
v5 v6 v7 v8
v9 v10 v11 securinseparase securindegradation
securin:separase separase degradation Net1P dephosphorylation Net1 phosphorylation v15
v16 Net1Cdc14 phosphorylation v18 v19
v20 v21 v22 v23
v24 v25 v26 v27
v28 Tem1 degradation in MEN Cdc15 degradation in MEN  
Rules
Assignment Rule (variable: separase) Assignment Rule (variable: inactive Cdh1) Assignment Rule (variable: inactive Tem1) Assignment Rule (variable: securin)
Assignment Rule (variable: inactive Polo) Assignment Rule (variable: Cdk activity) Assignment Rule (variable: Net1P) Assignment Rule (variable: Cdc14)
Assignment Rule (variable: inactive Cdc15) Assignment Rule (variable: PP2A)    
Physical entities
Compartments Species
compartment AA Clb2 degr
Cdc20 Cdh1 inactive Cdh1
securinT securin separaseT
separase securin:separase Net1
Net1Cdc14 PoloT Polo
inactive Polo Tem1 inactive Tem1
Cdc15 inactive Cdc15 MEN
PP2A Net1P Cdc14
Global parameters
Cdk activity ksclb2 kdclb2 kadclb2
kaadclb2 kscdc20 kdcdc20 kadcdc20
kdcdh kadcdh kapcdh Jcdh
Cdh1T kssecurin kdsecurin kadsecurin
ksseparase kdseparase lasecurin ldsecurin
kad kd kp kap
Jnet lanet ldnet Net1T
Cdc14T kspolo kdpolo kadpolo
kapolo kaapolo kipolo Jpolo
katem kaatem kitem kaitem
Jtem1 Tem1T kacdc15 kaacdc15
kicdc15 kaicdc15 Jcdc15 lamen
ldmen Cdc15T kpp ki
PP2AT Inh    
Reactions (31)
 
 v1 [AA] ↔ [Clb2];  
 
 v2 [Clb2] ↔ [degr];   {Cdc20} , {Cdh1}
 
 v3 [AA] ↔ [Cdc20];  
 
 v4 [Cdc20] ↔ [degr];   {Cdh1}
 
 v5 [inactive Cdh1] ↔ [Cdh1];   {Cdc14}
 
 v6 [Cdh1] ↔ [inactive Cdh1];  
 
 v7 [AA] ↔ [securinT] + [securin];  
 
 v8 [securinT] + [securin] ↔ [degr];   {Cdc20}
 
 v9 [AA] ↔ [separaseT] + [separase];  
 
 v10 [separaseT] + [separase] ↔ [degr];  
 
 v11 [securin] + [separase] ↔ [securin:separase];  
 
 securinseparase securindegradation [securin:separase] ↔ [separase];   {Cdc20}
 
 securin:separase separase degradation [securin:separase] ↔ [securin];  
 
 Net1P dephosphorylation [Net1P] ↔ [Net1];   {Cdc14} , {Clb2} , {PP2A}
 
 Net1 phosphorylation [Net1] ↔ [Net1P];   {MEN} , {Net1Cdc14} , {Clb2}
 
 v15 [Net1] ↔ [Net1Cdc14];   {Cdc14}
 
 v16 [Net1Cdc14] ↔ [Net1];  
 
 Net1Cdc14 phosphorylation [Net1Cdc14] ↔ [Net1P];   {MEN} , {Net1} , {Clb2}
 
 v18 [AA] ↔ [PoloT] + [inactive Polo];  
 
 v19 [PoloT] + [inactive Polo] ↔ [degr];   {Cdh1}
 
 v20 [inactive Polo] ↔ [Polo];   {PoloT}
 
 v21 [Polo] ↔ [inactive Polo];  
 
 v22 [Polo] ↔ [degr];   {Cdh1}
 
 v23 [inactive Tem1] ↔ [Tem1];   {Polo}
 
 v24 [Tem1] ↔ [inactive Tem1];   {PP2A}
 
 v25 [inactive Cdc15] ↔ [Cdc15];   {Cdc14}
 
 v26 [Cdc15] ↔ [inactive Cdc15];  
 
 v27 [AA] ↔ [MEN];   {Tem1} , {Cdc15}
 
 v28 [MEN] ↔ [degr];  
 
 Tem1 degradation in MEN [MEN] ↔ ;   {Tem1} , {PP2A}
 
 Cdc15 degradation in MEN [MEN] ↔ ;   {Cdc15} , {Clb2}
 
Rules (10)
 
 Assignment Rule (name: separase) separase = separaseT-securinseparase
 
 Assignment Rule (name: Cdh1_i) inactive Cdh1 = Cdh1T-Cdh1
 
 Assignment Rule (name: Tem1_i) inactive Tem1 = Tem1T-Tem1
 
 Assignment Rule (name: securin) securin = securinT-securinseparase
 
 Assignment Rule (name: Polo_i) inactive Polo = PoloT-Polo
 
 Assignment Rule (name: Cdk) Cdk activity = Clb2/(1+Inh)
 
 Assignment Rule (name: Net1P) Net1P = Net1T-Net1-Net1Cdc14
 
 Assignment Rule (name: Cdc14) Cdc14 = Cdc14T-Net1Cdc14
 
 Assignment Rule (name: Cdc15_i) inactive Cdc15 = Cdc15T-Cdc15
 
 Assignment Rule (name: PP2A) PP2A = (1+kpp*ki*separase)/(1+ki*separase)*PP2AT
 
 compartment Spatial dimensions: 3.0  Compartment size: 1.0
 
 AA
Compartment: compartment
Initial concentration: 1.0
Constant
 
 Clb2
Compartment: compartment
Initial concentration: 0.997
 
 degr
Compartment: compartment
Initial concentration: 1.0
Constant
 
 Cdc20
Compartment: compartment
Initial concentration: 0.0
 
 Cdh1
Compartment: compartment
Initial concentration: 3.8E-5
 
  inactive Cdh1
Compartment: compartment
 
 securinT
Compartment: compartment
Initial concentration: 0.6
 
  securin
Compartment: compartment
 
 separaseT
Compartment: compartment
Initial concentration: 0.25
 
  separase
Compartment: compartment
 
 securin:separase
Compartment: compartment
Initial concentration: 0.248
 
 Net1
Compartment: compartment
Initial concentration: 0.098
 
 Net1Cdc14
Compartment: compartment
Initial concentration: 0.485
 
 PoloT
Compartment: compartment
Initial concentration: 0.99
 
 Polo
Compartment: compartment
Initial concentration: 0.945
 
  inactive Polo
Compartment: compartment
 
 Tem1
Compartment: compartment
Initial concentration: 0.00389
 
  inactive Tem1
Compartment: compartment
 
 Cdc15
Compartment: compartment
Initial concentration: 0.0257
 
  inactive Cdc15
Compartment: compartment
 
 MEN
Compartment: compartment
Initial concentration: 8.0E-6
 
  PP2A
Compartment: compartment
 
  Net1P
Compartment: compartment
 
  Cdc14
Compartment: compartment
 
Global Parameters (54)
 
   Cdk activity
Value: NaN
 
   ksclb2
Value: 0.03
Constant
 
   kdclb2
Value: 0.03
Constant
 
   kadclb2
Value: 0.2
Constant
 
   kaadclb2
Value: 2.0
Constant
 
   kscdc20
Value: 0.015
Constant
 
   kdcdc20
Value: 0.05
Constant
 
   kadcdc20
Value: 2.0
Constant
 
   kdcdh
Value: 0.01
Constant
 
   kadcdh
Value: 1.0
Constant
 
   kapcdh
Value: 1.0
Constant
 
   Jcdh
Value: 0.0015
Constant
 
   Cdh1T
Value: 1.0
Constant
 
   kssecurin
Value: 0.03
Constant
 
   kdsecurin
Value: 0.05
Constant
 
   kadsecurin
Value: 2.0
Constant
 
   ksseparase
Value: 0.0010
Constant
 
   kdseparase
Value: 0.0040
Constant
 
   lasecurin
Value: 500.0
Constant
 
   ldsecurin
Value: 1.0
Constant
 
   kad
Value: 0.1
Constant
 
   kd
Value: 0.45
Constant
 
   kp
Value: 0.4
Constant
 
   kap
Value: 2.0
Constant
 
   Jnet
Value: 0.2
Constant
 
   lanet
Value: 500.0
Constant
 
   ldnet
Value: 1.0
Constant
 
   Net1T
Value: 1.0
Constant
 
   Cdc14T
Value: 0.5
Constant
 
   kspolo
Value: 0.01
Constant
 
   kdpolo
Value: 0.01
Constant
 
   kadpolo
Value: 0.25
Constant
 
   kapolo
Constant
 
   kaapolo
Value: 0.5
Constant
 
   kipolo
Value: 0.1
Constant
 
   Jpolo
Value: 0.25
Constant
 
   katem
Constant
 
   kaatem
Value: 0.5
Constant
 
   kitem
Value: 0.1
Constant
 
   kaitem
Value: 1.0
Constant
 
   Jtem1
Value: 0.0050
Constant
 
   Tem1T
Value: 1.0
Constant
 
   kacdc15
Value: 0.02
Constant
 
   kaacdc15
Value: 0.5
Constant
 
   kicdc15
Constant
 
   kaicdc15
Value: 0.2
Constant
 
   Jcdc15
Value: 0.2
Constant
 
   lamen
Value: 10.0
Constant
 
   ldmen
Value: 0.1
Constant
 
   Cdc15T
Value: 1.0
Constant
 
   kpp
Value: 0.1
Constant
 
   ki
Value: 20.0
Constant
 
   PP2AT
Value: 1.0
Constant
 
   Inh
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000409

Curator's comment: (updated: 27 Jan 2012 12:21:15 GMT)

Figure 7B (wild type exit) of the reference publication has been reproduced here using Copasi v4.7 (Build 34).

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