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BIOMD0000000103 - Legewie2006_apoptosis_NC

 

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Reference Publication
Publication ID: 16978046
Legewie S, Blüthgen N, Herzel H.
Mathematical modeling identifies inhibitors of apoptosis as mediators of positive feedback and bistability.
PLoS Comput. Biol. 2006 Sep; 2(9): e120
Institute for Theoretical Biology, Humboldt University, Berlin, Germany. s.legewie@biologie.hu-berlin.de  [more]
Model
Original Model: BIOMD0000000103.xml.origin
Submitter: Nicolas Le Novère
Submission ID: MODEL8567941122
Submission Date: 23 Mar 2007 10:58:18 UTC
Last Modification Date: 05 Jul 2012 14:46:07 UTC
Creation Date: 20 Apr 2006 10:59:50 UTC
Encoders:  Harish Dharuri
   Stefan Legewie
   Nils Bluethgen
   Hanspeter Herzel
set #1
bqbiol:isPartOf KEGG Pathway hsa04210
bqbiol:isVersionOf Gene Ontology apoptotic process
bqbiol:occursIn Taxonomy cellular organisms
Notes

This model represents the non-competitive binding of XIAP to Casapase-3 and Caspase-9. In other words, XIAP mediated feedback is abolished in this model. The authors state that this leads to bistable-reversible behaviour as depicted in Fig 4C. The wild-type model displays a bistable-irreversible profile. This shows that irreversibility requires XIAP mediated feedback. The model was tested on MathSBML. However, please note that the paper does not contain any figure that corresponds to simulation of the Non-Competitive 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: 16978046 Submission Date: 23 Mar 2007 10:58:18 UTC Last Modification Date: 05 Jul 2012 14:46:07 UTC Creation Date: 20 Apr 2006 10:59:50 UTC
Mathematical expressions
Reactions
Caspase 9 / Apaf-1 binding Caspase 3 cleavage by Caspase 9 Caspase 3 cleavage by Caspase 9-Apaf-1 Caspase 9 Xiap binding
Caspase 9-Apaf-1 Xiap binding Caspase 9-Xiap Apaf-1 binding cleaved Caspase 3-Xiap binding Caspase 9 cleavage by cleaved caspase 3
Caspase 9 cleavage by cleaved caspase 3 when Apaf-1 is bound cleaved Caspase 9 Apaf-1 binding cleaved Caspase 9 XIAP binding cleaved Caspase 9-Apaf-1 XIAP binding
cleaved Caspase 9-Xiap Apaf-1 binding Caspase 3 cleavage by cleaved Caspase 9 Caspase 3 cleavage by cleaved Caspase 9 - Apaf-1 Apaf-1 turnover
Caspase 9 turnover Xiap turnover Caspase 9-Xiap degradation Apaf-1-Caspase 9-Xiap degradation
Apaf-1-Caspase 9 degradation Caspase 3 turnover Caspase 3 cleaved degradation Caspase 3 cleaved-Xiap degradation
Caspase 9 cleaved-Xiap degradation Caspase 9 cleaved degradation Apaf-1 Caspase 9 cleaved degradation Apaf-1 Caspase 9 cleaved-Xiap degradation
Caspase9-Xiap-Caspase3_star degradation Apaf-1-Caspase9-Xiap-Caspase3_star degradation Caspase9_star-Xiap-Caspase3_star degradation Apaf-1-Caspase9_star-Xiap-Caspase3_star degradation
Cleaved-Caspase 3 binding with Xiap-Caspase 9 Cleaved-Caspase 3 binding with Apaf-Xiap-Caspase 9 Cleaved-Caspase 3 binding with Cleaved-Xiap-Caspase 9 Apaf-Xiap-cleaved Caspase 9 binding with cleaved Caspase 3
Binding of Caspase 9 to cleaved Caspase 3-Xiap Binding of Apaf-Caspase 9 to cleaved Caspase 3-Xiap Binding of cleaved Caspase 9 to cleaved Caspase 3-Xiap Binding of cleaved Caspase 9-Apaf-1 to cleaved Caspase 3-Xiap
Binding of Caspase 9-Xiap-cleaved Caspase 3 with Apaf Binding of cleaved Caspase 9-Xiap-cleaved Caspase 3 with Apaf    
Physical entities
Compartments Species
Cytosol APAF-1 Caspase 9 Caspase 9-XIAP complex
XIAP APAF-1-Caspase 9-XIAP complex APAF-1-Caspase 9 complex
Caspase 3 Caspase 3 cleaved Caspase 3 cleaved - XIAP complex
Caspase 9 cleaved-XIAP complex Caspase 9 cleaved APAF-1-Caspase 9 cleaved complex
Apaf-1-Caspase 9 cleaved -XIAP complex Apaf-1-Caspase 9 cleaved -XIAP complex Apaf-1-Caspase 9 cleaved -XIAP complex
Apaf-1-Caspase 9 cleaved -XIAP complex Apaf-1-Caspase 9 cleaved -XIAP complex  
Global parameters
k1 kb1 k2 k3
k9 k9b k10 k10b
k13 k13b k15 k15b
k4 k5 k8 k8b
k11 k11b k12 k12b
k14 k14b k6 k7
k16 k16prod k17 k17prod
k18 k18prod k19 k20
k21 k22 k22prod k23
k24 k25 k26 k27
k28 k29 k30 k31
k32 a d k41
k42      
Reactions (42)
 
 Caspase 9 / Apaf-1 binding [APAF-1] + [Caspase 9] ↔ [APAF-1-Caspase 9 complex];  
 
 Caspase 3 cleavage by Caspase 9 [Caspase 3] + [Caspase 9] → [Caspase 3 cleaved] + [Caspase 9];  
 
 Caspase 3 cleavage by Caspase 9-Apaf-1 [Caspase 3] + [APAF-1-Caspase 9 complex] → [Caspase 3 cleaved] + [APAF-1-Caspase 9 complex];  
 
 Caspase 9 Xiap binding [Caspase 9] + [XIAP] ↔ [Caspase 9-XIAP complex];  
 
 Caspase 9-Apaf-1 Xiap binding [APAF-1-Caspase 9 complex] + [XIAP] ↔ [APAF-1-Caspase 9-XIAP complex];  
 
 Caspase 9-Xiap Apaf-1 binding [Caspase 9-XIAP complex] + [APAF-1] ↔ [APAF-1-Caspase 9-XIAP complex];  
 
 cleaved Caspase 3-Xiap binding [Caspase 3 cleaved] + [XIAP] ↔ [Caspase 3 cleaved - XIAP complex];  
 
 Caspase 9 cleavage by cleaved caspase 3 [Caspase 9] + [Caspase 3 cleaved] → [Caspase 9 cleaved] + [Caspase 3 cleaved];  
 
 Caspase 9 cleavage by cleaved caspase 3 when Apaf-1 is bound [APAF-1-Caspase 9 complex] + [Caspase 3 cleaved] → [APAF-1-Caspase 9 cleaved complex] + [Caspase 3 cleaved];  
 
 cleaved Caspase 9 Apaf-1 binding [Caspase 9 cleaved] + [APAF-1] ↔ [APAF-1-Caspase 9 cleaved complex];  
 
 cleaved Caspase 9 XIAP binding [Caspase 9 cleaved] + [XIAP] ↔ [Caspase 9 cleaved-XIAP complex];  
 
 cleaved Caspase 9-Apaf-1 XIAP binding [APAF-1-Caspase 9 cleaved complex] + [XIAP] ↔ [Apaf-1-Caspase 9 cleaved -XIAP complex];  
 
 cleaved Caspase 9-Xiap Apaf-1 binding [Caspase 9 cleaved-XIAP complex] + [APAF-1] ↔ [Apaf-1-Caspase 9 cleaved -XIAP complex];  
 
 Caspase 3 cleavage by cleaved Caspase 9 [Caspase 3] + [Caspase 9 cleaved] → [Caspase 3 cleaved] + [Caspase 9 cleaved];  
 
 Caspase 3 cleavage by cleaved Caspase 9 - Apaf-1 [Caspase 3] + [APAF-1-Caspase 9 cleaved complex] → [Caspase 3 cleaved] + [APAF-1-Caspase 9 cleaved complex];  
 
 Apaf-1 turnover  → [APAF-1];  
 
 Caspase 9 turnover  → [Caspase 9];  
 
 Xiap turnover  → [XIAP];  
 
 Caspase 9-Xiap degradation [Caspase 9-XIAP complex] → ;  
 
 Apaf-1-Caspase 9-Xiap degradation [APAF-1-Caspase 9-XIAP complex] → ;  
 
 Apaf-1-Caspase 9 degradation [APAF-1-Caspase 9 complex] → ;  
 
 Caspase 3 turnover  → [Caspase 3];  
 
 Caspase 3 cleaved degradation [Caspase 3 cleaved] → ;  
 
 Caspase 3 cleaved-Xiap degradation [Caspase 3 cleaved - XIAP complex] → ;  
 
 Caspase 9 cleaved-Xiap degradation [Caspase 9 cleaved-XIAP complex] → ;  
 
 Caspase 9 cleaved degradation [Caspase 9 cleaved] → ;  
 
 Apaf-1 Caspase 9 cleaved degradation [APAF-1-Caspase 9 cleaved complex] → ;  
 
 Apaf-1 Caspase 9 cleaved-Xiap degradation [Apaf-1-Caspase 9 cleaved -XIAP complex] → ;  
 
 Caspase9-Xiap-Caspase3_star degradation [Apaf-1-Caspase 9 cleaved -XIAP complex] → ;  
 
 Apaf-1-Caspase9-Xiap-Caspase3_star degradation [Apaf-1-Caspase 9 cleaved -XIAP complex] → ;  
 
 Caspase9_star-Xiap-Caspase3_star degradation [Apaf-1-Caspase 9 cleaved -XIAP complex] → ;  
 
 Apaf-1-Caspase9_star-Xiap-Caspase3_star degradation [Apaf-1-Caspase 9 cleaved -XIAP complex] → ;  
 
 Cleaved-Caspase 3 binding with Xiap-Caspase 9 [Caspase 3 cleaved] + [Caspase 9-XIAP complex] ↔ [Apaf-1-Caspase 9 cleaved -XIAP complex];  
 
 Cleaved-Caspase 3 binding with Apaf-Xiap-Caspase 9 [Caspase 3 cleaved] + [APAF-1-Caspase 9-XIAP complex] ↔ [Apaf-1-Caspase 9 cleaved -XIAP complex];  
 
 Cleaved-Caspase 3 binding with Cleaved-Xiap-Caspase 9 [Caspase 3 cleaved] + [Caspase 9 cleaved-XIAP complex] ↔ [Apaf-1-Caspase 9 cleaved -XIAP complex];  
 
 Apaf-Xiap-cleaved Caspase 9 binding with cleaved Caspase 3 [Caspase 3 cleaved] + [Apaf-1-Caspase 9 cleaved -XIAP complex] ↔ [Apaf-1-Caspase 9 cleaved -XIAP complex];  
 
 Binding of Caspase 9 to cleaved Caspase 3-Xiap [Caspase 9] + [Caspase 3 cleaved - XIAP complex] ↔ [Apaf-1-Caspase 9 cleaved -XIAP complex];  
 
 Binding of Apaf-Caspase 9 to cleaved Caspase 3-Xiap [APAF-1-Caspase 9 complex] + [Caspase 3 cleaved - XIAP complex] ↔ [Apaf-1-Caspase 9 cleaved -XIAP complex];  
 
 Binding of cleaved Caspase 9 to cleaved Caspase 3-Xiap [Caspase 9 cleaved] + [Caspase 3 cleaved - XIAP complex] ↔ [Apaf-1-Caspase 9 cleaved -XIAP complex];  
 
 Binding of cleaved Caspase 9-Apaf-1 to cleaved Caspase 3-Xiap [APAF-1-Caspase 9 cleaved complex] + [Caspase 3 cleaved - XIAP complex] ↔ [Apaf-1-Caspase 9 cleaved -XIAP complex];  
 
 Binding of Caspase 9-Xiap-cleaved Caspase 3 with Apaf [Apaf-1-Caspase 9 cleaved -XIAP complex] + [APAF-1] ↔ [Apaf-1-Caspase 9 cleaved -XIAP complex];  
 
 Binding of cleaved Caspase 9-Xiap-cleaved Caspase 3 with Apaf [Apaf-1-Caspase 9 cleaved -XIAP complex] + [APAF-1] ↔ [Apaf-1-Caspase 9 cleaved -XIAP complex];  
 
 Cytosol Spatial dimensions: 3.0  Compartment size: 1.0
 
 APAF-1
Compartment: Cytosol
Initial concentration: 20.0
 
 Caspase 9
Compartment: Cytosol
Initial concentration: 20.0
 
 Caspase 9-XIAP complex
Compartment: Cytosol
Initial concentration: 0.0
 
 XIAP
Compartment: Cytosol
Initial concentration: 40.0
 
 APAF-1-Caspase 9-XIAP complex
Compartment: Cytosol
Initial concentration: 0.0
 
 APAF-1-Caspase 9 complex
Compartment: Cytosol
Initial concentration: 0.0
 
 Caspase 3
Compartment: Cytosol
Initial concentration: 200.0
 
 Caspase 3 cleaved
Compartment: Cytosol
Initial concentration: 0.0
 
 Caspase 3 cleaved - XIAP complex
Compartment: Cytosol
Initial concentration: 0.0
 
 Caspase 9 cleaved-XIAP complex
Compartment: Cytosol
Initial concentration: 0.0
 
 Caspase 9 cleaved
Compartment: Cytosol
Initial concentration: 0.0
 
 APAF-1-Caspase 9 cleaved complex
Compartment: Cytosol
Initial concentration: 0.0
 
 Apaf-1-Caspase 9 cleaved -XIAP complex
Compartment: Cytosol
Initial concentration: 0.0
 
 Apaf-1-Caspase 9 cleaved -XIAP complex
Compartment: Cytosol
Initial concentration: 0.0
 
 Apaf-1-Caspase 9 cleaved -XIAP complex
Compartment: Cytosol
Initial concentration: 0.0
 
 Apaf-1-Caspase 9 cleaved -XIAP complex
Compartment: Cytosol
Initial concentration: 0.0
 
 Apaf-1-Caspase 9 cleaved -XIAP complex
Compartment: Cytosol
Initial concentration: 0.0
 
Global Parameters (49)
 
   k1
Value: 0.0020
Constant
 
   kb1
Value: 0.1
Constant
 
   k2
Value: 5.0E-6
Constant
 
   k3
Value: 3.5E-4
Constant
 
   k9
Value: 0.0010
Constant
 
   k9b
Value: 0.0010
Constant
 
   k10
Value: 0.0010
Constant
 
   k10b
Value: 0.0010
Constant
 
   k13
Value: 0.0020
Constant
 
   k13b
Value: 0.1
Constant
 
   k15
Value: 0.0030
Constant
 
   k15b
Value: 0.0010
Constant
 
   k4
Value: 2.0E-4
Constant
 
   k5
Value: 2.0E-4
Constant
 
   k8
Value: 0.0020
Constant
 
   k8b
Value: 0.1
Constant
 
   k11
Value: 0.0010
Constant
 
   k11b
Value: 0.0010
Constant
 
   k12
Value: 0.0010
Constant
 
   k12b
Value: 0.0010
Constant
 
   k14
Value: 0.0020
Constant
 
   k14b
Value: 0.1
Constant
 
   k6
Value: 5.0E-5
Constant
 
   k7
Value: 0.0035
Constant
 
   k16
Value: 0.0010
Constant
 
   k16prod
Value: 0.02
Constant
 
   k17
Value: 0.0010
Constant
 
   k17prod
Value: 0.02
Constant
 
   k18
Value: 0.0010
Constant
 
   k18prod
Value: 0.04
Constant
 
   k19
Value: 0.0010
Constant
 
   k20
Value: 0.0010
Constant
 
   k21
Value: 0.0010
Constant
 
   k22
Value: 0.0010
Constant
 
   k22prod
Value: 0.2
Constant
 
   k23
Value: 0.0010
Constant
 
   k24
Value: 0.0010
Constant
 
   k25
Value: 0.0010
Constant
 
   k26
Value: 0.0010
Constant
 
   k27
Value: 0.0010
Constant
 
   k28
Value: 0.0010
Constant
 
   k29
Value: 0.0010
Constant
 
   k30
Value: 0.0010
Constant
 
   k31
Value: 0.0010
Constant
 
   k32
Value: 0.0010
Constant
 
   a
Value: 1.0
Constant
 
   d
Value: 1.0
Constant
 
   k41
Value: 1.0
Constant
 
   k42
Value: 1.0
Constant
 
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