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BIOMD0000000406 - Moriya2011_CellCycle_FissionYeast

 

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Reference Publication
Publication ID: 22146300
Moriya H, Chino A, Kapuy O, Csikász-Nagy A, Novák B.
Overexpression limits of fission yeast cell-cycle regulators in vivo and in silico.
Mol. Syst. Biol. 2011; 7: 556
Research Core for Interdisciplinary Sciences, Okayama University, Okayama, Japan.  [more]
Model
Original Model: BIOMD0000000111
Submitter: Hisao Moriya
Submission ID: MODEL1111040000
Submission Date: 04 Nov 2011 04:16:34 UTC
Last Modification Date: 11 Jul 2012 18:10:05 UTC
Creation Date: 12 Jan 2012 13:27:10 UTC
Encoders:  Vijayalakshmi Chelliah
   Hisao Moriya
set #1
bqbiol:occursIn Taxonomy Schizosaccharomyces pombe
set #2
bqbiol:isVersionOf Gene Ontology regulation of cell cycle
set #3
bqmodel:isDerivedFrom BioModels Database Kaizu2010_BuddingYeastCellCycle_Map
Notes

This model is from the article:
Overexpression limits of fission yeast cell-cycle regulators in vivo and in silico.
Moriya H, Chino A, Kapuy O, Csikász-Nagy A, Novák B. Mol Syst Biol. 2011 Dec 6;7:556. 22146300 ,
Abstract:
Cellular systems are generally robust against fluctuations of intracellular parameters such as gene expression level. However, little is known about expression limits of genes required to halt cellular systems. In this study, using the fission yeast Schizosaccharomyces pombe, we developed a genetic 'tug-of-war' (gTOW) method to assess the overexpression limit of certain genes. Using gTOW, we determined copy number limits for 31 cell-cycle regulators; the limits varied from 1 to >100. Comparison with orthologs of the budding yeast Saccharomyces cerevisiae suggested the presence of a conserved fragile core in the eukaryotic cell cycle. Robustness profiles of networks regulating cytokinesis in both yeasts (septation-initiation network (SIN) and mitotic exit network (MEN)) were quite different, probably reflecting differences in their physiologic functions. Fragility in the regulation of GTPase spg1 was due to dosage imbalance against GTPase-activating protein (GAP) byr4. Using the gTOW data, we modified a mathematical model and successfully reproduced the robustness of the S. pombe cell cycle with the model.


To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not.


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: 22146300 Submission Date: 04 Nov 2011 04:16:34 UTC Last Modification Date: 11 Jul 2012 18:10:05 UTC Creation Date: 12 Jan 2012 13:27:10 UTC
Mathematical expressions
Reactions
re3 re4 re5 re6
re7 re8 Cdc13_Synthesis Trim_Dissociation_Rum1degradation
re15 Trim_Dissociation_Rum1degradation re17 Cdc13_Dephosphorylation
Cdc13_Synthesis Cdc13_Phosphorylation Cdc13_Dephosphorylation Rum1+Cdc13_association
re23 Rum1+Cdc13_association re25 Cdc13_Dephosphorylation
re28 re29 re30 re31
re32 re33 re34 re35
re36 re37 re38 re39
re40 re41 re42 re43
re44 re45 re46 re47
re48 re53 re54 re56
re57 re58 re60 re62
re66 re67 re68  
Rules
Assignment Rule (variable: BB) Assignment Rule (variable: kwee) Assignment Rule (variable: Vdrum) Assignment Rule (variable: Vdcyc)
Assignment Rule (variable: Vdc18) Assignment Rule (variable: k25) Assignment Rule (variable: chrom) Assignment Rule (variable: preRC)
Assignment Rule (variable: Cdc18) Assignment Rule (variable: UDNA)    
Physical entities
Compartments Species
default Vdrum Vdcyc sa4_degraded
Srw1 Slp1A Puc1
IE iIE rum1+
cig2+ Cdc13 cdc13+
pCdc13 sa161_degraded Cig2p
Pyp3 iSrw1 iSlp1
Cig2 iCdc10 Cdc10
Mik1 mik1+ sa347_degraded
Cig1 cig1+ sa353_degraded
Clp1+ iWee1 Wee1
Clp1 iCdc25 Cdc25
Cdc18T cdc18+ sa386_degraded
preRC postRC repldna
irepldna sa370_degraded sa44_degraded
Vdc18 Cdc13p-Rum1 Cig2-Rum1
Cig2p-Rum1 UDNA Cdc13-Rum1
Rum1    
Global parameters
ksc18' ksc18 kdc18 kdc18c13
kdc18cig kdc18cig' krepl kini_dash
kini'' kini''' ko18 ko18r
kori kipre kipre' Jipre
n k k' kscyc
kdcyc kdcycsrw kdcycsrw' kdcycslp
kdcycslp' kasrw kasrw' kisrw
kisrw' kisrw'' kisrw''' kisrw''''
Jasrw Jisrw kaslp kislp
Jaslp Jislp kaie kiie
Jaie Jiie ksrum kdrum
kdrumpuc kdrumci1 kdrumcig kdrumcig_dash
kdrumc13 kdrumc13' lp lm
kscig' kdcig kdcig' kac10
kic10 kic10' Jac10 Jic10
kwee' kwee'' Vawee' Vawee''
Viwee' Viwee'' Jawee Jiwee
k25' k25'' Va25'' Vi25''
Vi25' Vi25 Ja25 Ji25
lcp lcm kmik' kmik''
Vamik Vimik Vimik' Vimik''
Vimik''' kpyp ksflp ksflp'
kdflp ksci1 kdci1 kdci1'
kdci1'' k255 kpyp2 kscig
oriT BB chrom UDNA
kmik Vdrum Vdcyc Vdc18
k25 Vamik' preRC Rad3
beta Puc1 Srw1T Slp1T
Cdc10T Cdc25T Wee1T kaie'
Cdc18 kwee    
Reactions (51)
 
 re3 [iSrw1] → [Srw1];   {Slp1A}
 
 re4 [Srw1] → [iSrw1];   {Cdc13} , {Puc1} , {Cig1} , {Cig2}
 
 re5 [iIE] → [IE];   {Cig1} , {Cdc13}
 
 re6 [IE] → [iIE];  
 
 re7 [iSlp1] → [Slp1A];   {IE}
 
 re8 [Slp1A] → [iSlp1];  
 
 Cdc13_Synthesis [cdc13+] → [Cdc13];  
 
 Trim_Dissociation_Rum1degradation [Cdc13p-Rum1] → [pCdc13] + [sa161_degraded];   {Vdrum}
 
 re15 [Cdc13-Rum1] → [Rum1] + [sa4_degraded];   {Vdcyc}
 
 Trim_Dissociation_Rum1degradation [Cdc13-Rum1] → [Cdc13] + [sa161_degraded];   {Vdrum}
 
 re17 [Cdc13p-Rum1] → [Rum1] + [sa4_degraded];   {Vdcyc}
 
 Cdc13_Dephosphorylation [Cdc13p-Rum1] → [Cdc13-Rum1];   {Pyp3} , {Cdc25}
 
 Cdc13_Synthesis [cig2+] → [Cig2];   {Cdc10}
 
 Cdc13_Phosphorylation [Cig2] → [Cig2p];   {Mik1}
 
 Cdc13_Dephosphorylation [Cig2p] → [Cig2];   {Pyp3} , {Cdc25} , {UDNA}
 
 Rum1+Cdc13_association [Rum1] + [Cig2] ↔ [Cig2-Rum1];  
 
 re23 [Cig2-Rum1] → [Rum1] + [sa44_degraded];   {Slp1A}
 
 Rum1+Cdc13_association [Rum1] + [Cig2p] ↔ [Cig2p-Rum1];  
 
 re25 [Cig2p-Rum1] → [Rum1] + [sa44_degraded];   {Slp1A}
 
 Cdc13_Dephosphorylation [Cig2p-Rum1] → [Cig2-Rum1];   {Pyp3} , {Cdc25}
 
 re28 [Cig2] → [sa44_degraded];   {Slp1A}
 
 re29 [Cig2p-Rum1] → [Cig2p];   {Vdrum}
 
 re30 [Cig2-Rum1] → [Cig2] + [sa161_degraded];   {Vdrum}
 
 re31 [Cig2p] → [sa44_degraded];   {Slp1A}
 
 re32 [Cdc10] → [iCdc10];   {Cig2}
 
 re33 [iCdc10] → [Cdc10];  
 
 re34 [mik1+] → [Mik1];   {Cdc10}
 
 re35 [Mik1] → [sa347_degraded];   {Cig2} , {Cdc13} , {pCdc13}
 
 re36 [cig1+] → [Cig1];  
 
 re37 [Cig1] → [sa353_degraded];   {Slp1A} , {Srw1}
 
 re38 [Clp1+] → [Clp1];   {Slp1A}
 
 re39 [iWee1] → [Wee1];   {Clp1}
 
 re40 [Wee1] → [iWee1];   {Cdc13}
 
 re41 [pCdc13] → [sa4_degraded];   {Vdcyc}
 
 re42 [Cdc13] → [sa4_degraded];   {Vdcyc}
 
 re43 [Cdc13-Rum1] → [Cdc13p-Rum1];   {Wee1} , {Mik1}
 
 re44 [Cig2-Rum1] → [Cig2p-Rum1];   {Mik1}
 
 re45 [iCdc25] → [Cdc25];   {Cdc13}
 
 re46 [Cdc25] → [iCdc25];   {Clp1} , {UDNA}
 
 re47 [cdc18+] → [Cdc18T];   {Cdc10}
 
 re48 [Cdc18T] → [sa386_degraded];   {Vdc18}
 
 re53 [Clp1] → [sa370_degraded];  
 
 re54 [Cdc13] + [Rum1] ↔ [Cdc13-Rum1];  
 
 re56 [pCdc13] → [Cdc13];   {Cdc25} , {Pyp3}
 
 re57 [Cdc13] → [pCdc13];   {Wee1} , {Mik1}
 
 re58 [Rum1] + [pCdc13] ↔ [Cdc13p-Rum1];  
 
 re60 [Rum1] → [sa161_degraded];   {Vdrum}
 
 re62 [rum1+] → [Rum1];  
 
 re66 [preRC] → [postRC];   {Cig2} , {Cdc13} , {Cig2p}
 
 re67 [repldna] → [irepldna];   {Cig2} , {Cdc13} , {Cig2p}
 
 re68 [postRC] → [repldna];  
 
Rules (10)
 
 Assignment Rule (name: BB) BB = oriT+s84+(ko18r+Vdc18)/ko18
 
 Assignment Rule (name: kwee) kwee = kwee_dash*Wee1T+(kwee_dash2-kwee_dash)*s80
 
 Assignment Rule (name: Vdrum) Vdrum = kdrum+kdrumpuc*Puc1+kdrumci1*s75+kdrumcig*s67+kdrumcig_dash*s63+kdrumc13*s56+kdrumc13_dash*s60
 
 Assignment Rule (name: Vdcyc) Vdcyc = kdcyc+kdcycsrw*s47+kdcycsrw_dash*Srw1T+kdcycslp*s48+kdcycslp_dash*Slp1T
 
 Assignment Rule (name: Vdc18) Vdc18 = kdc18+kdc18c13*s56+kdc18cig*s67+kdc18cig_dash*s63
 
 Assignment Rule (name: k25) k25 = k25_dash*Cdc25T+(k25_dash2-k25_dash)*s83
 
 Assignment Rule (name: chrom) chrom = 2*oriT*s84/(BB+(BB^2-4*oriT*s84)^(0.5))
 
 Assignment Rule (name: preRC) preRC = (oriT-s90-s91)*Cdc18/((ko18r+Vdc18)/ko18+Cdc18)
 
 Assignment Rule (name: Cdc18) Cdc18 = s84-chrom
 
 Assignment Rule (name: UDNA) UDNA = Rad3*(k*s84+k_dash*s90*Cdc18/((ko18r+Vdc18)/ko18+Cdc18))
 
  Spatial dimensions: 3.0  Compartment size: 1.0  (Units: volume)
 
 Vdrum
Compartment: default
Initial amount: 0.0
Constant
 
 Vdcyc
Compartment: default
Initial amount: 0.0
Constant
 
 sa4_degraded
Compartment: default
Initial amount: 0.0
 
 Srw1
Compartment: default
Initial amount: 0.00239076
 
 Slp1A
Compartment: default
Initial amount: 6.33821E-5
 
 Puc1
Compartment: default
Initial amount: 0.0
 
 IE
Compartment: default
Initial amount: 0.00127807
 
 iIE
Compartment: default
Initial amount: 0.0
 
 rum1+
Compartment: default
Initial amount: 0.0
 
 cig2+
Compartment: default
Initial amount: 0.0
 
 Cdc13
Compartment: default
Initial amount: 0.0439902
 
 cdc13+
Compartment: default
Initial amount: 0.0
 
 pCdc13
Compartment: default
Initial amount: 0.1147007
 
 sa161_degraded
Compartment: default
Initial amount: 0.0
 
 Cig2p
Compartment: default
Initial amount: 0.0
 
 Pyp3
Compartment: default
Initial amount: 0.0
 
 iSrw1
Compartment: default
Initial amount: 0.0
 
 iSlp1
Compartment: default
Initial amount: 0.0
 
 Cig2
Compartment: default
Initial amount: 0.0
 
 iCdc10
Compartment: default
Initial amount: 0.0
 
 Cdc10
Compartment: default
Initial amount: 0.0
 
 Mik1
Compartment: default
Initial amount: 0.0
 
 mik1+
Compartment: default
Initial amount: 0.0
 
 sa347_degraded
Compartment: default
Initial amount: 0.0
 
 Cig1
Compartment: default
Initial amount: 0.0
 
 cig1+
Compartment: default
Initial amount: 0.0
 
 sa353_degraded
Compartment: default
Initial amount: 0.0
 
 Clp1+
Compartment: default
Initial amount: 0.0
 
 iWee1
Compartment: default
Initial amount: 0.0
Constant
 
 Wee1
Compartment: default
Initial amount: 0.0
 
 Clp1
Compartment: default
Initial amount: 0.0
 
 iCdc25
Compartment: default
Initial amount: 0.0
 
 Cdc25
Compartment: default
Initial amount: 0.0
 
 Cdc18T
Compartment: default
Initial amount: 0.0
 
 cdc18+
Compartment: default
Initial amount: 0.0
 
 sa386_degraded
Compartment: default
Initial amount: 0.0
 
 preRC
Compartment: default
Initial amount: 0.0
 
 postRC
Compartment: default
Initial amount: 0.0
 
 repldna
Compartment: default
Initial amount: 0.0
 
 irepldna
Compartment: default
Initial amount: 0.0
 
 sa370_degraded
Compartment: default
Initial amount: 0.0
 
 sa44_degraded
Compartment: default
Initial amount: 0.0
 
 Vdc18
Compartment: default
Initial amount: 0.0
 
 Cdc13p-Rum1
Compartment: default
Initial amount: 0.0432273
 
 Cig2-Rum1
Compartment: default
Initial amount: 0.0
 
 Cig2p-Rum1
Compartment: default
Initial amount: 0.0
 
 UDNA
Compartment: default
Initial amount: 0.0
Constant
 
 Cdc13-Rum1
Compartment: default
Initial amount: 0.0165018
 
 Rum1
Compartment: default
Initial amount: 0.0
 
Global Parameters (118)
 
 ksc18'
Value: 0.075
Constant
 
 ksc18
Value: 0.0050
Constant
 
 kdc18
Value: 0.0010
Constant
 
 kdc18c13
Value: 0.45
Constant
 
 kdc18cig
Value: 1.0
Constant
 
 kdc18cig'
Constant
 
 krepl
Value: 2.0
Constant
 
 kini_dash
Value: 10.0
Constant
 
 kini''
Value: 10.0
Constant
 
 kini'''
Constant
 
 ko18
Value: 100.0
Constant
 
 ko18r
Value: 1.0
Constant
 
 kori
Value: 125.0
Constant
 
 kipre
Value: 1.0
Constant
 
 kipre'
Value: 1.0
Constant
 
 Jipre
Value: 0.01
Constant
 
 n
Value: 4.0
Constant
 
 k
Value: 0.1
Constant
 
 k'
Value: 10.0
Constant
 
 kscyc
Value: 0.03
Constant
 
 kdcyc
Value: 0.018
Constant
 
 kdcycsrw
Value: 1.0
Constant
 
 kdcycsrw'
Value: 1.0E-4
Constant
 
 kdcycslp
Value: 1.0
Constant
 
 kdcycslp'
Value: 3.0E-4
Constant
 
 kasrw
Value: 1.25
Constant
 
 kasrw'
Value: 30.0
Constant
 
 kisrw
Value: 1.5
Constant
 
 kisrw'
Value: 40.0
Constant
 
 kisrw''
Value: 1.0
Constant
 
 kisrw'''
Value: 4.0
Constant
 
 kisrw''''
Value: 4.0
Constant
 
 Jasrw
Value: 0.01
Constant
 
 Jisrw
Value: 0.01
Constant
 
 kaslp
Value: 1.0
Constant
 
 kislp
Value: 0.2
Constant
 
 Jaslp
Value: 0.01
Constant
 
 Jislp
Value: 0.01
Constant
 
 kaie
Value: 0.0975
Constant
 
 kiie
Value: 0.04
Constant
 
 Jaie
Value: 0.01
Constant
 
 Jiie
Value: 0.01
Constant
 
 ksrum
Value: 1.0
Constant
 
 kdrum
Value: 0.4
Constant
 
 kdrumpuc
Value: 0.1
Constant
 
 kdrumci1
Value: 1.0
Constant
 
 kdrumcig
Value: 15.0
Constant
 
 kdrumcig_dash
Value: 10.0
Constant
 
 kdrumc13
Value: 50.0
Constant
 
 kdrumc13'
Value: 5.0
Constant
 
 lp
Value: 500.0
Constant
 
 lm
Value: 100.0
Constant
 
 kscig'
Value: 0.04
Constant
 
 kdcig
Value: 0.02
Constant
 
 kdcig'
Value: 1.0
Constant
 
 kac10
Value: 0.125
Constant
 
 kic10
Value: 0.01
Constant
 
 kic10'
Value: 3.0
Constant
 
 Jac10
Value: 0.01
Constant
 
 Jic10
Value: 0.01
Constant
 
 kwee'
Value: 0.01
Constant
 
 kwee''
Value: 0.5
Constant
 
 Vawee'
Value: 0.24
Constant
 
 Vawee''
Value: 1.0
Constant
 
 Viwee'
Constant
 
 Viwee''
Value: 1.0
Constant
 
 Jawee
Value: 0.04
Constant
 
 Jiwee
Value: 0.03
Constant
 
 k25'
Value: 0.01
Constant
 
 k25''
Value: 1.0
Constant
 
 Va25''
Value: 1.0
Constant
 
 Vi25''
Value: 1.0
Constant
 
 Vi25'
Value: 0.24
Constant
 
 Vi25
Value: 0.3
Constant
 
 Ja25
Value: 0.03
Constant
 
 Ji25
Value: 0.03
Constant
 
 lcp
Value: 3.0
Constant
 
 lcm
Value: 1.0
Constant
 
 kmik'
Value: 0.01
Constant
 
 kmik''
Value: 4.0
Constant
 
 Vamik
Value: 0.25
Constant
 
 Vimik
Value: 0.75
Constant
 
 Vimik'
Value: 10.0
Constant
 
 Vimik''
Value: 10.0
Constant
 
 Vimik'''
Value: 0.25
Constant
 
 kpyp
Value: 0.6
Constant
 
 ksflp
Value: 0.0015
Constant
 
 ksflp'
Value: 0.015
Constant
 
 kdflp
Value: 0.1
Constant
 
 ksci1
Value: 0.0015
Constant
 
 kdci1
Value: 0.1
Constant
 
 kdci1'
Value: 5.0
Constant
 
 kdci1''
Value: 0.2
Constant
 
 k255
Value: 0.1
Constant
 
 kpyp2
Value: 0.01
Constant
 
 kscig
Value: 0.0020
Constant
 
 oriT
Value: 1.0
Constant
 
   BB  
 
   chrom  
 
   UDNA  
 
 kmik  
 
   Vdrum  
 
   Vdcyc  
 
   Vdc18  
 
   k25  
 
 Vamik'
Value: 0.75
Constant
 
   preRC  
 
 Rad3
Value: 1.0
Constant
 
 beta
Value: 10.0
Constant
 
 Puc1
Value: 1.0
Constant
 
 Srw1T
Value: 1.0
Constant
 
 Slp1T
Value: 1.0
Constant
 
 Cdc10T
Value: 1.0
Constant
 
 Cdc25T
Value: 1.0
Constant
 
 Wee1T
Value: 1.0
Constant
 
 kaie'
Value: 0.05
Constant
 
   Cdc18  
 
   kwee  
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000406

Curator's comment: (updated: 12 Jan 2012 13:26:37 GMT)

This model correspond to the gTOW (genetic tug-of-war) Model described in the paper. Figure 7c of the reference publication has been reproduced here, using Copasi v4.7 (Build 34).

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