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BIOMD0000000297 - Ciliberto2003_Morphogenesis_Checkpoint

 

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Reference Publication
Publication ID: 14691135
Ciliberto A, Novak B, Tyson JJ.
Mathematical model of the morphogenesis checkpoint in budding yeast.
J. Cell Biol. 2003 Dec; 163(6): 1243-1254
Department of Biology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.  [more]
Model
Original Model: BIOMD0000000297.origin
Submitter: Harish Dharuri
Submission ID: MODEL2504064544
Submission Date: 17 Mar 2008 10:26:57 UTC
Last Modification Date: 31 Jan 2012 13:52:48 UTC
Creation Date: 07 Feb 2008 14:15:40 UTC
Encoders:  Harish Dharuri
   Vijayalakshmi Chelliah
set #1
bqbiol:isPartOf KEGG Pathway Cell cycle - yeast
bqbiol:isVersionOf Gene Ontology anatomical structure morphogenesis
Gene Ontology obsolete cytokinesis after mitosis checkpoint
set #2
bqbiol:occursIn Taxonomy Schizosaccharomyces pombe
Notes

This a model from the article:
Mathematical model of the morphogenesis checkpoint in budding yeast.
Ciliberto A, Novak B, Tyson JJ J. Cell Biol. [2003 Dec; Volume: 163 (Issue: 6 )] Page info: 1243-54 14691135 ,
Abstract:
The morphogenesis checkpoint in budding yeast delays progression through the cell cycle in response to stimuli that prevent bud formation. Central to the checkpoint mechanism is Swe1 kinase: normally inactive, its activation halts cell cycle progression in G2. We propose a molecular network for Swe1 control, based on published observations of budding yeast and analogous control signals in fission yeast. The proposed Swe1 network is merged with a model of cyclin-dependent kinase regulation, converted into a set of differential equations and studied by numerical simulation. The simulations accurately reproduce the phenotypes of a dozen checkpoint mutants. Among other predictions, the model attributes a new role to Hsl1, a kinase known to play a role in Swe1 degradation: Hsl1 must also be indirectly responsible for potent inhibition of Swe1 activity. The model supports the idea that the morphogenesis checkpoint, like other checkpoints, raises the cell size threshold for progression from one phase of the cell cycle to the next.

The model reproduces Fig 3 of the paper.

This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 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: 14691135 Submission Date: 17 Mar 2008 10:26:57 UTC Last Modification Date: 31 Jan 2012 13:52:48 UTC Creation Date: 07 Feb 2008 14:15:40 UTC
Mathematical expressions
Reactions
Clb-Sic dissociation Clb2 removal from complex Sic1 removal from complex Phosphorylation of Cdc28-Clb2-Sic1 complex
Complex formation Dephosphorylation of complex Clb2 degradation Clb2 phosphorylation
Clb2 synthesis Clb2 dephosphorylation SBF inhibition SBF synthesis
IE inhibition IE synthesis Cdc20 deactivation activated Cdc20 degradation
Cdc20 activation Cdh1inhibition Cdh1 synthesis Swe1 modification
Phosphorylated Swe1 modification Swe1 phosphorylation Swe1M phosphorylation Swe1 degradation
Swe1 production from its modified form PSwe1 production from its modified form PSwe1 dephosphorylation PSwe1M dephosphorylation
SBF dependent Swe1 synthesis Swe1 synthesis PSwe1 degradation PTrim complex dissociation
Sic1 dissociation from PTrim complex PClb dissociation from PTrim complex PTrim complex formation Mih1a inhibition
Mih1a synthesis Mcm inhibition Mcm synthesis BE degradation
BE formation Sic1 degradation Sic1 synthesis Cln degradation
SBF dependent Cln synthesis Swe1M degradation Cdc20 degradation Clb2 dependent Cdc20 synthesis
PSwe1M degradation PClb degradation cell mass  
Rules
Assignment Rule (variable: kswe) Assignment Rule (variable: kmih) Assignment Rule (variable: Swe1T) Assignment Rule (variable: IEin)
Assignment Rule (variable: Cdh1in) Assignment Rule (variable: Mih1) Assignment Rule (variable: Mcmin) Assignment Rule (variable: SBFin)
Events
event_0000002 event_0000004 event_0000003 event_0000005
Physical entities
Compartments Species
compartment CDC28_Clb2_Sic1_Complex Clb2 Sic1
Phosphorylated Cdc28_Clb2_Sic1 Complex Phosphorylated Clb2 SBF
Intermediary Enzyme Cdc20 activated Cdc20
Cdh1 Swe1 Swe1 modified
Phosphorylated Swe1 Phosphorylated Swe1M Mih1a
Mcm BE Cln
mass    
Global parameters
kswe kswe_prime kswe_doubleprime kswe_tripleprime
kmih kmih_prime Mih_ast kmih_doubleprime
Mih IEin IEtot Cdh1in
Cdh1tot Mih1 Mih1tot Mcmin
Mcmtot SBFin SBFtot kdiss
kdsic_prime kdsic_doubleprime kdsic kdclb_doubleprime
kdclb_tripleprime kdclb_prime kass ksclb
Jm eps kisbf_prime kisbf_doubleprime
jisbf kasbf_prime kasbf_doubleprime jasbf
kiie jiie kaie jaie
kicdc20 jicdc20 kdcdc20 kacdc20
jacdc20 kicdh kicdh_prime jicdh
Kacdh_prime Kacdh_doubleprime jacdh khsl1
BUD Viwee Jiwee kdswe_prime
khsl1r Vawee Jawee ksswe
kssweC Vimih jimih Vamih
Jamih kimcm jimcm kamcm
jamcm kdbud ksbud kssic
kdcln kscln kscdc20_prime kscdc20_doubleprime
jscdc20 kdswe_doubleprime mu flag
Swe1T      
Reactions (51)
 
 Clb-Sic dissociation [CDC28_Clb2_Sic1_Complex] → [Sic1] + [Clb2];  
 
 Clb2 removal from complex [CDC28_Clb2_Sic1_Complex] → [Clb2];   {Cln}
 
 Sic1 removal from complex [CDC28_Clb2_Sic1_Complex] → [Sic1];   {Cdh1} , {Cdc20 activated}
 
 Phosphorylation of Cdc28-Clb2-Sic1 complex [CDC28_Clb2_Sic1_Complex] → [Phosphorylated Cdc28_Clb2_Sic1 Complex];  
 
 Complex formation [Sic1] + [Clb2] → [CDC28_Clb2_Sic1_Complex];  
 
 Dephosphorylation of complex [Phosphorylated Cdc28_Clb2_Sic1 Complex] → [CDC28_Clb2_Sic1_Complex];  
 
 Clb2 degradation [Clb2] → ;   {Cdh1} , {Cdc20 activated}
 
 Clb2 phosphorylation [Clb2] → [Phosphorylated Clb2];  
 
 Clb2 synthesis  → [Clb2];   {mass} , {Mcm}
 
 Clb2 dephosphorylation [Phosphorylated Clb2] → [Clb2];  
 
 SBF inhibition [SBF] → ;   {Clb2}
 
 SBF synthesis  → [SBF];   {mass} , {Cln}
 
 IE inhibition [Intermediary Enzyme] → ;  
 
 IE synthesis  → [Intermediary Enzyme];   {Clb2}
 
 Cdc20 deactivation [Cdc20 activated] → [Cdc20];  
 
 activated Cdc20 degradation [Cdc20 activated] → ;  
 
 Cdc20 activation [Cdc20] → [Cdc20 activated];   {Intermediary Enzyme}
 
 Cdh1inhibition [Cdh1] → ;   {Clb2} , {Cln}
 
 Cdh1 synthesis  → [Cdh1];   {Cdc20 activated}
 
 Swe1 modification [Swe1] → [Swe1 modified];  
 
 Phosphorylated Swe1 modification [Phosphorylated Swe1] → [Phosphorylated Swe1M];  
 
 Swe1 phosphorylation [Swe1] → [Phosphorylated Swe1];   {Clb2}
 
 Swe1M phosphorylation [Swe1 modified] → [Phosphorylated Swe1M];   {Clb2}
 
 Swe1 degradation [Swe1] → ;  
 
 Swe1 production from its modified form [Swe1 modified] → [Swe1];  
 
 PSwe1 production from its modified form [Phosphorylated Swe1M] → [Phosphorylated Swe1];  
 
 PSwe1 dephosphorylation [Phosphorylated Swe1] → [Swe1];  
 
 PSwe1M dephosphorylation [Phosphorylated Swe1M] → [Swe1 modified];  
 
 SBF dependent Swe1 synthesis  → [Swe1];   {SBF}
 
 Swe1 synthesis  → [Swe1];  
 
 PSwe1 degradation [Phosphorylated Swe1] → ;  
 
 PTrim complex dissociation [Phosphorylated Cdc28_Clb2_Sic1 Complex] → [Phosphorylated Clb2] + [Sic1];  
 
 Sic1 dissociation from PTrim complex [Phosphorylated Cdc28_Clb2_Sic1 Complex] → [Sic1];   {Cdh1} , {Cdc20 activated}
 
 PClb dissociation from PTrim complex [Phosphorylated Cdc28_Clb2_Sic1 Complex] → [Phosphorylated Clb2];   {Cln} , {Clb2}
 
 PTrim complex formation [Sic1] + [Phosphorylated Clb2] → [Phosphorylated Cdc28_Clb2_Sic1 Complex];  
 
 Mih1a inhibition [Mih1a] → ;  
 
 Mih1a synthesis  → [Mih1a];   {Clb2}
 
 Mcm inhibition [Mcm] → ;  
 
 Mcm synthesis  → [Mcm];   {Clb2}
 
 BE degradation [BE] → ;  
 
 BE formation  → [BE];   {Cln}
 
 Sic1 degradation [Sic1] → ;   {Cln} , {Clb2}
 
 Sic1 synthesis  → [Sic1];  
 
 Cln degradation [Cln] → ;  
 
 SBF dependent Cln synthesis  → [Cln];   {SBF}
 
 Swe1M degradation [Swe1 modified] → ;  
 
 Cdc20 degradation [Cdc20] → ;  
 
 Clb2 dependent Cdc20 synthesis  → [Cdc20];   {Clb2}
 
 PSwe1M degradation [Phosphorylated Swe1M] → ;  
 
 PClb degradation [Phosphorylated Clb2] → ;   {Cdh1} , {Cdc20 activated}
 
 cell mass  → [mass];  
 
Rules (8)
 
 Assignment Rule (name: kswe) kswe = kswe_prime*Swe1+kswe_doubleprime*Swe1M+kswe_tripleprime*PSwe1
 
 Assignment Rule (name: kmih) kmih = kmih_prime*Mih_ast+kmih_doubleprime*Mih
 
 Assignment Rule (name: Swe1T) Swe1T = Swe1+Swe1M+PSwe1+PSwe1M
 
 Assignment Rule (name: IEin) IEin = IEtot-IE
 
 Assignment Rule (name: Cdh1in) Cdh1in = Cdh1tot-Cdh1
 
 Assignment Rule (name: Mih1) Mih1 = Mih1tot-Mih1a
 
 Assignment Rule (name: Mcmin) Mcmin = Mcmtot-Mcm
 
 Assignment Rule (name: SBFin) SBFin = SBFtot-SBF
 
Events (4)
 
 event_0000002
flag = 1
 
 event_0000004
BE = 0
mass = 0.5*mass
 
 event_0000003
BUD = 1
 
 event_0000005
BUD = 0
 
  Spatial dimensions: 3.0  Compartment size: 1.0
 
 CDC28_Clb2_Sic1_Complex
Compartment: compartment
Initial concentration: 0.084410675
 
 Clb2
Compartment: compartment
Initial concentration: 0.18453673
 
 Sic1
Compartment: compartment
Initial concentration: 0.0035491784
 
 Phosphorylated Cdc28_Clb2_Sic1 Complex
Compartment: compartment
Initial concentration: 1.402314E-5
 
 Phosphorylated Clb2
Compartment: compartment
Initial concentration: 3.0203049E-5
 
 SBF
Compartment: compartment
Initial concentration: 0.12405464
 
 Intermediary Enzyme
Compartment: compartment
Initial concentration: 0.52220768
 
 Cdc20 activated
Compartment: compartment
Initial concentration: 1.4384692
 
 Cdc20
Compartment: compartment
Initial concentration: 1.1722378
 
 Cdh1
Compartment: compartment
Initial concentration: 0.99263656
 
 Swe1
Compartment: compartment
Initial concentration: 3.1588585E-4
 
 Swe1 modified
Compartment: compartment
Initial concentration: 0.018360127
 
 Phosphorylated Swe1
Compartment: compartment
Initial concentration: 2.0500785E-4
 
 Phosphorylated Swe1M
Compartment: compartment
Initial concentration: 0.013336782
 
 Mih1a
Compartment: compartment
Initial concentration: 0.80809075
 
 Mcm
Compartment: compartment
Initial concentration: 0.93289256
 
 BE
Compartment: compartment
Initial concentration: 2.4296179E-4
 
 Cln
Compartment: compartment
Initial concentration: 0.053600963
 
 mass
Compartment: compartment
Initial concentration: 0.80224854
 
Global Parameters (81)
 
  kswe  
 
 kswe_prime
Value: 2.0
Constant
 
 kswe_doubleprime
Value: 0.01
Constant
 
 kswe_tripleprime
Value: 0.2
Constant
 
  kmih  
 
 kmih_prime
Value: 5.0
Constant
 
 Mih_ast
Constant
 
 kmih_doubleprime
Value: 0.5
Constant
 
 Mih
Constant
 
  IEin  
 
 IEtot
Value: 1.0
Constant
 
  Cdh1in  
 
 Cdh1tot
Value: 1.0
Constant
 
  Mih1  
 
 Mih1tot
Value: 1.0
Constant
 
  Mcmin  
 
 Mcmtot
Value: 1.0
Constant
 
  SBFin  
 
 SBFtot
Value: 1.0
Constant
 
 kdiss
Value: 0.1
Constant
 
 kdsic_prime
Value: 1.0
Constant
 
 kdsic_doubleprime
Value: 3.0
Constant
 
 kdsic
Value: 0.01
Constant
 
 kdclb_doubleprime
Value: 1.0
Constant
 
 kdclb_tripleprime
Value: 0.1
Constant
 
 kdclb_prime
Value: 0.015
Constant
 
 kass
Value: 300.0
Constant
 
 ksclb
Value: 0.015
Constant
 
 Jm
Value: 10.0
Constant
 
 eps
Value: 0.5
Constant
 
 kisbf_prime
Value: 1.0
Constant
 
 kisbf_doubleprime
Value: 2.0
Constant
 
 jisbf
Value: 0.01
Constant
 
 kasbf_prime
Value: 1.0
Constant
 
 kasbf_doubleprime
Constant
 
 jasbf
Value: 0.01
Constant
 
 kiie
Value: 0.04
Constant
 
 jiie
Value: 0.01
Constant
 
 kaie
Value: 0.1
Constant
 
 jaie
Value: 0.01
Constant
 
 kicdc20
Value: 0.25
Constant
 
 jicdc20
Value: 0.0010
Constant
 
 kdcdc20
Value: 0.1
Constant
 
 kacdc20
Value: 1.0
Constant
 
 jacdc20
Value: 0.0010
Constant
 
 kicdh
Value: 35.0
Constant
 
 kicdh_prime
Value: 2.0
Constant
 
 jicdh
Value: 0.01
Constant
 
 Kacdh_prime
Value: 1.0
Constant
 
 Kacdh_doubleprime
Value: 10.0
Constant
 
 jacdh
Value: 0.01
Constant
 
 khsl1
Value: 1.0
Constant
 
   BUD  
 
 Viwee
Value: 1.0
Constant
 
 Jiwee
Value: 0.05
Constant
 
 kdswe_prime
Value: 0.0070
Constant
 
 khsl1r
Value: 0.01
Constant
 
 Vawee
Value: 0.3
Constant
 
 Jawee
Value: 0.05
Constant
 
 ksswe
Value: 0.0025
Constant
 
 kssweC
Constant
 
 Vimih
Value: 0.3
Constant
 
 jimih
Value: 0.1
Constant
 
 Vamih
Value: 1.0
Constant
 
 Jamih
Value: 0.1
Constant
 
 kimcm
Value: 0.15
Constant
 
 jimcm
Value: 0.1
Constant
 
 kamcm
Value: 1.0
Constant
 
 jamcm
Value: 0.1
Constant
 
 kdbud
Value: 0.1
Constant
 
 ksbud
Value: 0.1
Constant
 
 kssic
Value: 0.1
Constant
 
 kdcln
Value: 0.1
Constant
 
 kscln
Value: 0.1
Constant
 
 kscdc20_prime
Value: 0.0050
Constant
 
 kscdc20_doubleprime
Value: 0.3
Constant
 
 jscdc20
Value: 0.3
Constant
 
 kdswe_doubleprime
Value: 0.05
Constant
 
 mu
Value: 0.0050
Constant
 
   flag  
 
  Swe1T  
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000297

Curator's comment: (updated: 13 Jan 2011 13:22:22 GMT)

Figure 3 of the reference publication has been reproduced. The model was integrated and simulated using Copasi v4.6 (Build 32).

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