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BIOMD0000000286 - Proctor2010 - a link between GSK3 and p53 in Alzheimer's Disease

 

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Reference Publication
Publication ID: 20181016
Proctor CJ, Gray DA.
GSK3 and p53 - is there a link in Alzheimer's disease?
Mol Neurodegener 2010; 5: 7
Centre for Integrated Systems Biology of Ageing and Nutrition, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, NE4 5PL, UK. c.j.proctor@ncl.ac.uk.  [more]
Model
Original Model: 
Submitter: Carole Proctor
Submission ID: MODEL0910130002
Submission Date: 03 Nov 2009 16:35:40 UTC
Last Modification Date: 10 Oct 2014 11:16:03 UTC
Creation Date: 27 Jan 2010 11:31:35 UTC
Encoders:  Lukas Endler
   Vijayalakshmi Chelliah
   Carole J Proctor
set #1
bqmodel:isDerivedFrom BioModels Database Proctor2008_p53_Mdm2_ARF
BioModels Database Proctor2008_p53_Mdm2_ATM
BioModels Database Proctor2007_ubiquitine
set #2
bqbiol:isVersionOf Gene Ontology inclusion body assembly
Gene Ontology DNA damage response, signal transduction by p53 class mediator
set #3
bqbiol:isPartOf KEGG Pathway Alzheimer's disease
set #4
bqbiol:hasTaxon Taxonomy Mammalia
set #5
bqbiol:hasProperty Human Disease Ontology Alzheimer's disease
Notes

This is the model described the article:
GSK3 and p53 - is there a link in Alzheimer's disease?
Carole J Proctor and Douglas A Gray Molecular Neurodegeneration 2010, 5:7; doi: 10.1186/1750-1326-5-7
Abstract:
Background: Recent evidence suggests that glycogen synthase kinase-3beta (GSK3beta) is implicated in both sporadic and familial forms of Alzheimer's disease. The transcription factor, p53 also plays a role and has been linked to an increase in tau hyperphosphorylation although the effect is indirect. There is also evidence that GSK3beta and p53 interact and that the activity of both proteins is increased as a result of this interaction. Under normal cellular conditions, p53 is kept at low levels by Mdm2 but when cells are stressed, p53 is stabilised and may then interact with GSK3beta. We propose that this interaction has an important contribution to cellular outcomes and to test this hypothesis we developed a stochastic simulation model.
Results: The model predicts that high levels of DNA damage leads to increased activity of p53 and GSK3beta and low levels of aggregation but if DNA damage is repaired, the aggregates are eventually cleared. The model also shows that over long periods of time, aggregates may start to form due to stochastic events leading to increased levels of ROS and damaged DNA. This is followed by increased activity of p53 and GSK3beta and a vicious cycle ensues.
Conclusions: Since p53 and GSK3beta are both involved in the apoptotic pathway, and GSK3beta overactivity leads to increased levels of plaques and tangles, our model might explain the link between protein aggregation and neuronal loss in neurodegeneration.


Notes: The original model submitted by the author had events in it. Since, this model is intended for Stochastic Simulation run and Copasi cannot handle events in Stochastic run, I have replaced the events with piecewise assignment rule. -Viji

This model is an extension of Proctor_p53_Mdm2_ATM ( BIOMD0000000188 ).

This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2010 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: 20181016 Submission Date: 03 Nov 2009 16:35:40 UTC Last Modification Date: 10 Oct 2014 11:16:03 UTC Creation Date: 27 Jan 2010 11:31:35 UTC
Mathematical expressions
Reactions
p53mRNASynthesis p53mRNADegradation Mdm2Synthesis Mdm2mRNASynthesis1
Mdm2mRNASynthesis2 Mdm2mRNASynthesis3 Mdm2mRNASynthesis4 Mdm2mRNADegradation
P53Mdm2Binding P53Mdm2Release GSK3p53Binding GSK3p53Release
GSK3p53PBinding GSK3_p53PRelease E1UbBinding E2UbBinding
Mdm2Ubiquitination Mdm2polyUbiquitination1 Mdm2polyUbiquitination2 Mdm2polyUbiquitination3
Mdm2Deubiquitination4 Mdm2Deubiquitination3 Mdm2Deubiquitination2 Mdm2Deubiquitination1
Mdm2ProteasomeBinding1 Mdm2Degradation p53Synthesis p53Monoubiquitination
p53Polyubiquitination1 p53Polyubiquitination2 p53Polyubiquitination3 p53Deubiqutination4
p53Deubiquitination3 p53Deubiquitination2 p53Deubiquitination1 Mdm2GSK3phosphorylation1
Mdm2GSK3phosphorylation2 Mdm2GSK3phosphorylation3 p53ProteasomeBinding1 Degradationp53_Ub4
TauMTbinding TauMTrelease Tauphosphorylation1 Tauphosphorylation2
Tauphosphorylation3 Tauphosphorylation4 Tauphosphorylation5 Tauphosphorylation6
Taudephosphorylation1 Taudephosphorylation2 TauP1Aggregation1 TauP1Aggregation2
TauP2Aggregation1 TauP2Aggregation2 TauAggregation1 TauAggregation2
TangleFormation1 TangleFormation2 ProteasomeInhibitionAggTau Abetaproduction1
Abetaproduction2 ProteasomeInhibitionAbeta AbetaDegradation AbetaAggregation1
AbetaAggregation2 AbetaPlaqueFormation1 AbetaPlaqueFormation2 p53transcriptionViaAbeta
DNAdamage DNArepair ATMactivation p53phosphorylation
p53dephosphorylation Mdm2phosphorylation Mdm2dephosphorylation Mdm2PUbiquitination
Mdm2PpolyUbiquitination1 Mdm2PpolyUbiquitination2 Mdm2PpolyUbiquitination3 Mdm2PDeubiquitination4
Mdm2PDeubiquitination3 Mdm2PDeubiquitination2 Mdm2PDeubiquitination1 Mdm2PProteasomeBinding1
Mdm2PDegradation ATMInactivation AggAbetaROSproduction1 AggAbetaROSproduction2
ROSDNAdamage basalROSDNAdamage TauSynthesis TauProteasomeBinding
Tau20SProteasomeDegradation      
Rules
Assignment Rule (variable: IR) Assignment Rule (variable: tot_mdm2) Assignment Rule (variable: tot_p53)  
Physical entities
Compartments Species
cell Mdm2 p53 Mdm2_p53
Mdm2_mRNA p53_mRNA ATMA
ATMI p53_P Mdm2_P
IR ROS basalROS
damDNA E1 E2
E1_Ub E2_Ub Proteasome
Ub p53DUB Mdm2DUB
DUB Mdm2_p53_Ub Mdm2_p53_Ub2
Mdm2_p53_Ub3 Mdm2_p53_Ub4 Mdm2_P1_p53_Ub4
Mdm2_Ub Mdm2_Ub2 Mdm2_Ub3
Mdm2_Ub4 Mdm2_P_Ub Mdm2_P_Ub2
Mdm2_P_Ub3 Mdm2_P_Ub4 p53_Ub4_Proteasome
Mdm2_Ub4_Proteasome Mdm2_P_Ub4_Proteasome GSK3b
GSK3b_p53 GSK3b_p53_P Abeta
AggAbeta_Proteasome AggAbeta AbetaPlaque
Tau Tau_P1 Tau_P2
MT_Tau AggTau AggTau_Proteasome
Proteasome_Tau PP1 NFT
ATP ADP AMP
Source Sink  
Global parameters
ksynp53mRNA kdegp53mRNA ksynMdm2mRNA kdegMdm2mRNA
ksynMdm2mRNAGSK3bp53 ksynp53 kdegp53 kbinMdm2p53
krelMdm2p53 kbinGSK3bp53 krelGSK3bp53 ksynMdm2
kdegMdm2 kbinE1Ub kbinE2Ub kp53Ub
kp53PolyUb kbinProt kactDUBp53 kactDUBProtp53
kactDUBMdm2 kMdm2Ub kMdm2PUb kMdm2PolyUb
kdam krepair kactATM kinactATM
kphosp53 kdephosp53 kphosMdm2 kdephosMdm2
kphosMdm2GSK3b kphosMdm2GSK3bp53 kphospTauGSK3bp53 kphospTauGSK3b
kdephospTau kbinMTTau krelMTTau ksynTau
kbinTauProt kdegTau20SProt kaggTau kaggTauP1
kaggTauP2 ktangfor kprodAbeta kinhibprot
kdegAbeta kaggAbeta kpf ksynp53mRNAAbeta
kdamROS kdamBasalROS kgenROSAbeta kproteff
tot_mdm2 tot_p53    
Reactions (93)
 
 p53mRNASynthesis [Source] → [p53_mRNA];  
 
 p53mRNADegradation [p53_mRNA] → [Sink];  
 
 Mdm2Synthesis [Mdm2_mRNA] → [Mdm2_mRNA] + [Mdm2];  
 
 Mdm2mRNASynthesis1 [p53] → [p53] + [Mdm2_mRNA];  
 
 Mdm2mRNASynthesis2 [p53_P] → [p53_P] + [Mdm2_mRNA];  
 
 Mdm2mRNASynthesis3 [GSK3b_p53] → [GSK3b_p53] + [Mdm2_mRNA];  
 
 Mdm2mRNASynthesis4 [GSK3b_p53_P] → [GSK3b_p53_P] + [Mdm2_mRNA];  
 
 Mdm2mRNADegradation [Mdm2_mRNA] → [Sink];  
 
 P53Mdm2Binding [p53] + [Mdm2] → [Mdm2_p53];  
 
 P53Mdm2Release [Mdm2_p53] → [p53] + [Mdm2];  
 
 GSK3p53Binding [GSK3b] + [p53] → [GSK3b_p53];  
 
 GSK3p53Release [GSK3b_p53] → [GSK3b] + [p53];  
 
 GSK3p53PBinding [GSK3b] + [p53_P] → [GSK3b_p53_P];  
 
 GSK3_p53PRelease [GSK3b_p53_P] → [GSK3b] + [p53_P];  
 
 E1UbBinding [E1] + [Ub] + [ATP] → [E1_Ub] + [AMP];  
 
 E2UbBinding [E2] + [E1_Ub] → [E2_Ub] + [E1];  
 
 Mdm2Ubiquitination [Mdm2] + [E2_Ub] → [Mdm2_Ub] + [E2];  
 
 Mdm2polyUbiquitination1 [Mdm2_Ub] + [E2_Ub] → [Mdm2_Ub2] + [E2];  
 
 Mdm2polyUbiquitination2 [Mdm2_Ub2] + [E2_Ub] → [Mdm2_Ub3] + [E2];  
 
 Mdm2polyUbiquitination3 [Mdm2_Ub3] + [E2_Ub] → [Mdm2_Ub4] + [E2];  
 
 Mdm2Deubiquitination4 [Mdm2_Ub4] + [Mdm2DUB] → [Mdm2_Ub3] + [Mdm2DUB] + [Ub];  
 
 Mdm2Deubiquitination3 [Mdm2_Ub3] + [Mdm2DUB] → [Mdm2_Ub2] + [Mdm2DUB] + [Ub];  
 
 Mdm2Deubiquitination2 [Mdm2_Ub2] + [Mdm2DUB] → [Mdm2_Ub] + [Mdm2DUB] + [Ub];  
 
 Mdm2Deubiquitination1 [Mdm2_Ub] + [Mdm2DUB] → [Mdm2] + [Mdm2DUB] + [Ub];  
 
 Mdm2ProteasomeBinding1 [Mdm2_Ub4] + [Proteasome] → [Mdm2_Ub4_Proteasome];  
 
 Mdm2Degradation [Mdm2_Ub4_Proteasome] → [Proteasome] + 4.0 × [Ub];  
 
 p53Synthesis [p53_mRNA] → [p53] + [p53_mRNA];  
 
 p53Monoubiquitination [E2_Ub] + [Mdm2_p53] → [Mdm2_p53_Ub] + [E2];  
 
 p53Polyubiquitination1 [Mdm2_p53_Ub] + [E2_Ub] → [Mdm2_p53_Ub2] + [E2];  
 
 p53Polyubiquitination2 [Mdm2_p53_Ub2] + [E2_Ub] → [Mdm2_p53_Ub3] + [E2];  
 
 p53Polyubiquitination3 [Mdm2_p53_Ub3] + [E2_Ub] → [Mdm2_p53_Ub4] + [E2];  
 
 p53Deubiqutination4 [Mdm2_p53_Ub4] + [p53DUB] → [Mdm2_p53_Ub3] + [p53DUB] + [Ub];  
 
 p53Deubiquitination3 [Mdm2_p53_Ub3] + [p53DUB] → [Mdm2_p53_Ub2] + [p53DUB] + [Ub];  
 
 p53Deubiquitination2 [Mdm2_p53_Ub2] + [p53DUB] → [Mdm2_p53_Ub] + [p53DUB] + [Ub];  
 
 p53Deubiquitination1 [Mdm2_p53_Ub] + [p53DUB] → [Mdm2_p53] + [p53DUB] + [Ub];  
 
 Mdm2GSK3phosphorylation1 [Mdm2_p53_Ub4] + [GSK3b] → [Mdm2_P1_p53_Ub4] + [GSK3b];  
 
 Mdm2GSK3phosphorylation2 [Mdm2_p53_Ub4] + [GSK3b_p53] → [Mdm2_P1_p53_Ub4] + [GSK3b_p53];  
 
 Mdm2GSK3phosphorylation3 [Mdm2_p53_Ub4] + [GSK3b_p53_P] → [Mdm2_P1_p53_Ub4] + [GSK3b_p53_P];  
 
 p53ProteasomeBinding1 [Mdm2_P1_p53_Ub4] + [Proteasome] → [p53_Ub4_Proteasome] + [Mdm2];  
 
 Degradationp53_Ub4 [p53_Ub4_Proteasome] + [ATP] → 4.0 × [Ub] + [Proteasome] + [ADP];  
 
 TauMTbinding [Tau] → [MT_Tau];  
 
 TauMTrelease [MT_Tau] → [Tau];  
 
 Tauphosphorylation1 [GSK3b_p53] + [Tau] → [GSK3b_p53] + [Tau_P1];  
 
 Tauphosphorylation2 [GSK3b_p53] + [Tau_P1] → [GSK3b_p53] + [Tau_P2];  
 
 Tauphosphorylation3 [GSK3b_p53_P] + [Tau] → [GSK3b_p53_P] + [Tau_P1];  
 
 Tauphosphorylation4 [GSK3b_p53_P] + [Tau_P1] → [GSK3b_p53_P] + [Tau_P2];  
 
 Tauphosphorylation5 [GSK3b] + [Tau] → [GSK3b] + [Tau_P1];  
 
 Tauphosphorylation6 [GSK3b] + [Tau_P1] → [GSK3b] + [Tau_P2];  
 
 Taudephosphorylation1 [Tau_P2] + [PP1] → [Tau_P1] + [PP1];  
 
 Taudephosphorylation2 [Tau_P1] + [PP1] → [Tau] + [PP1];  
 
 TauP1Aggregation1 2.0 × [Tau_P1] → 2.0 × [AggTau];  
 
 TauP1Aggregation2 [Tau_P1] + [AggTau] → 2.0 × [AggTau];  
 
 TauP2Aggregation1 2.0 × [Tau_P2] → 2.0 × [AggTau];  
 
 TauP2Aggregation2 [Tau_P2] + [AggTau] → 2.0 × [AggTau];  
 
 TauAggregation1 2.0 × [Tau] → 2.0 × [AggTau];  
 
 TauAggregation2 [Tau] + [AggTau] → 2.0 × [AggTau];  
 
 TangleFormation1 2.0 × [AggTau] → 2.0 × [NFT];  
 
 TangleFormation2 [AggTau] + [NFT] → 2.0 × [NFT];  
 
 ProteasomeInhibitionAggTau [AggTau] + [Proteasome] → [AggTau_Proteasome];  
 
 Abetaproduction1 [GSK3b_p53] → [Abeta] + [GSK3b_p53];  
 
 Abetaproduction2 [GSK3b_p53_P] → [Abeta] + [GSK3b_p53_P];  
 
 ProteasomeInhibitionAbeta [AggAbeta] + [Proteasome] → [AggAbeta_Proteasome];  
 
 AbetaDegradation [Abeta] → [Sink];  
 
 AbetaAggregation1 2.0 × [Abeta] → [AggAbeta];  
 
 AbetaAggregation2 [Abeta] + [AggAbeta] → 2.0 × [AggAbeta];  
 
 AbetaPlaqueFormation1 2.0 × [AggAbeta] → 2.0 × [AbetaPlaque];  
 
 AbetaPlaqueFormation2 [AggAbeta] + [AbetaPlaque] → 2.0 × [AbetaPlaque];  
 
 p53transcriptionViaAbeta [Abeta] → [p53_mRNA] + [Abeta];  
 
 DNAdamage  → [damDNA];   {IR}
 
 DNArepair [damDNA] → [Sink];  
 
 ATMactivation [damDNA] + [ATMI] → [damDNA] + [ATMA];  
 
 p53phosphorylation [p53] + [ATMA] → [p53_P] + [ATMA];  
 
 p53dephosphorylation [p53_P] → [p53];  
 
 Mdm2phosphorylation [Mdm2] + [ATMA] → [Mdm2_P] + [ATMA];  
 
 Mdm2dephosphorylation [Mdm2_P] → [Mdm2];  
 
 Mdm2PUbiquitination [Mdm2_P] + [E2_Ub] → [Mdm2_P_Ub] + [E2];  
 
 Mdm2PpolyUbiquitination1 [Mdm2_P_Ub] + [E2_Ub] → [Mdm2_P_Ub2] + [E2];  
 
 Mdm2PpolyUbiquitination2 [Mdm2_P_Ub2] + [E2_Ub] → [Mdm2_P_Ub3] + [E2];  
 
 Mdm2PpolyUbiquitination3 [Mdm2_P_Ub3] + [E2_Ub] → [Mdm2_P_Ub4] + [E2];  
 
 Mdm2PDeubiquitination4 [Mdm2_P_Ub4] + [Mdm2DUB] → [Mdm2_P_Ub3] + [Mdm2DUB] + [Ub];  
 
 Mdm2PDeubiquitination3 [Mdm2_P_Ub3] + [Mdm2DUB] → [Mdm2_P_Ub2] + [Mdm2DUB] + [Ub];  
 
 Mdm2PDeubiquitination2 [Mdm2_P_Ub2] + [Mdm2DUB] → [Mdm2_P_Ub] + [Mdm2DUB] + [Ub];  
 
 Mdm2PDeubiquitination1 [Mdm2_P_Ub] + [Mdm2DUB] → [Mdm2_P] + [Mdm2DUB] + [Ub];  
 
 Mdm2PProteasomeBinding1 [Mdm2_P_Ub4] + [Proteasome] → [Mdm2_P_Ub4_Proteasome];  
 
 Mdm2PDegradation [Mdm2_P_Ub4_Proteasome] → [Proteasome] + 4.0 × [Ub];  
 
 ATMInactivation [ATMA] → [ATMI];  
 
 AggAbetaROSproduction1 [AggAbeta] → [AggAbeta] + [ROS];  
 
 AggAbetaROSproduction2 [AggAbeta_Proteasome] → [AggAbeta_Proteasome] + [ROS];  
 
 ROSDNAdamage [ROS] → [ROS] + [damDNA];  
 
 basalROSDNAdamage [basalROS] → [basalROS] + [damDNA];  
 
 TauSynthesis [Source] → [Tau];  
 
 TauProteasomeBinding [Tau] + [Proteasome] → [Proteasome_Tau];  
 
 Tau20SProteasomeDegradation [Proteasome_Tau] → [Proteasome];  
 
Rules (3)
 
 Assignment Rule (name: IR) IR = piecewise(25, (t >= 3600) && (t <= 3660), 0)
 
 Assignment Rule (name: tot_mdm2) tot_mdm2 = Mdm2+Mdm2_p53+Mdm2_P+Mdm2_p53_Ub+Mdm2_p53_Ub2+Mdm2_p53_Ub3+Mdm2_p53_Ub4+Mdm2_P1_p53_Ub4+Mdm2_Ub+Mdm2_Ub2+Mdm2_Ub3+Mdm2_Ub4+Mdm2_P_Ub+Mdm2_P_Ub2+Mdm2_P_Ub3+Mdm2_P_Ub4+Mdm2_Ub4_Proteasome+Mdm2_P_Ub4_Proteasome
 
 Assignment Rule (name: tot_p53) tot_p53 = p53+Mdm2_p53+p53_P+Mdm2_p53_Ub+Mdm2_p53_Ub2+Mdm2_p53_Ub3+Mdm2_p53_Ub4+Mdm2_P1_p53_Ub4+p53_Ub4_Proteasome
 
  Spatial dimensions: 3.0  Compartment size: 1.0
 
 Mdm2
Compartment: cell
Initial amount: 5.0
 
 p53
Compartment: cell
Initial amount: 5.0
 
 Mdm2_p53
Compartment: cell
Initial amount: 95.0
 
 Mdm2_mRNA
Compartment: cell
Initial amount: 10.0
 
 p53_mRNA
Compartment: cell
Initial amount: 10.0
 
 ATMA
Compartment: cell
Initial amount: 0.0
 
 ATMI
Compartment: cell
Initial amount: 200.0
 
 p53_P
Compartment: cell
Initial amount: 0.0
 
 Mdm2_P
Compartment: cell
Initial amount: 0.0
 
  IR
Compartment: cell
Initial amount: 0.0
 
 ROS
Compartment: cell
Initial amount: 0.0
 
 basalROS
Compartment: cell
Initial amount: 10.0
 
 damDNA
Compartment: cell
Initial amount: 0.0
 
 E1
Compartment: cell
Initial amount: 100.0
 
 E2
Compartment: cell
Initial amount: 100.0
 
 E1_Ub
Compartment: cell
Initial amount: 0.0
 
 E2_Ub
Compartment: cell
Initial amount: 0.0
 
 Proteasome
Compartment: cell
Initial amount: 500.0
 
 Ub
Compartment: cell
Initial amount: 4000.0
 
 p53DUB
Compartment: cell
Initial amount: 200.0
 
 Mdm2DUB
Compartment: cell
Initial amount: 200.0
 
 DUB
Compartment: cell
Initial amount: 200.0
 
 Mdm2_p53_Ub
Compartment: cell
Initial amount: 0.0
 
 Mdm2_p53_Ub2
Compartment: cell
Initial amount: 0.0
 
 Mdm2_p53_Ub3
Compartment: cell
Initial amount: 0.0
 
 Mdm2_p53_Ub4
Compartment: cell
Initial amount: 0.0
 
 Mdm2_P1_p53_Ub4
Compartment: cell
Initial amount: 0.0
 
 Mdm2_Ub
Compartment: cell
Initial amount: 0.0
 
 Mdm2_Ub2
Compartment: cell
Initial amount: 0.0
 
 Mdm2_Ub3
Compartment: cell
Initial amount: 0.0
 
 Mdm2_Ub4
Compartment: cell
Initial amount: 0.0
 
 Mdm2_P_Ub
Compartment: cell
Initial amount: 0.0
 
 Mdm2_P_Ub2
Compartment: cell
Initial amount: 0.0
 
 Mdm2_P_Ub3
Compartment: cell
Initial amount: 0.0
 
 Mdm2_P_Ub4
Compartment: cell
Initial amount: 0.0
 
 p53_Ub4_Proteasome
Compartment: cell
Initial amount: 0.0
 
 Mdm2_Ub4_Proteasome
Compartment: cell
Initial amount: 0.0
 
 Mdm2_P_Ub4_Proteasome
Compartment: cell
Initial amount: 0.0
 
 GSK3b
Compartment: cell
Initial amount: 500.0
 
 GSK3b_p53
Compartment: cell
Initial amount: 0.0
 
 GSK3b_p53_P
Compartment: cell
Initial amount: 0.0
 
 Abeta
Compartment: cell
Initial amount: 0.0
 
 AggAbeta_Proteasome
Compartment: cell
Initial amount: 0.0
 
 AggAbeta
Compartment: cell
Initial amount: 0.0
 
 AbetaPlaque
Compartment: cell
Initial amount: 0.0
 
 Tau
Compartment: cell
Initial amount: 0.0
 
 Tau_P1
Compartment: cell
Initial amount: 0.0
 
 Tau_P2
Compartment: cell
Initial amount: 0.0
 
 MT_Tau
Compartment: cell
Initial amount: 100.0
 
 AggTau
Compartment: cell
Initial amount: 0.0
 
 AggTau_Proteasome
Compartment: cell
Initial amount: 0.0
 
 Proteasome_Tau
Compartment: cell
Initial amount: 0.0
 
 PP1
Compartment: cell
Initial amount: 50.0
 
 NFT
Compartment: cell
Initial amount: 0.0
 
 ATP
Compartment: cell
Initial amount: 10000.0
Constant
 
 ADP
Compartment: cell
Initial amount: 1000.0
Constant
 
 AMP
Compartment: cell
Initial amount: 1000.0
Constant
 
 Source
Compartment: cell
Initial amount: 1.0
Constant
 
 Sink
Compartment: cell
Initial amount: 0.0
Constant
 
Global Parameters (58)
 
 ksynp53mRNA
Value: 0.001
Constant
 
 kdegp53mRNA
Value: 1.0E-4
Constant
 
 ksynMdm2mRNA
Value: 5.0E-4
Constant
 
 kdegMdm2mRNA
Value: 5.0E-4
Constant
 
 ksynMdm2mRNAGSK3bp53
Value: 7.0E-4
Constant
 
 ksynp53
Value: 0.007
Constant
 
 kdegp53
Value: 0.005
Constant
 
 kbinMdm2p53
Value: 0.001155
Constant
 
 krelMdm2p53
Value: 1.155E-5
Constant
 
 kbinGSK3bp53
Value: 2.0E-6
Constant
 
 krelGSK3bp53
Value: 0.002
Constant
 
 ksynMdm2
Value: 4.95E-4
Constant
 
 kdegMdm2
Value: 0.01
Constant
 
 kbinE1Ub
Value: 2.0E-4
Constant
 
 kbinE2Ub
Value: 0.001
Constant
 
 kp53Ub
Value: 5.0E-5
Constant
 
 kp53PolyUb
Value: 0.01
Constant
 
 kbinProt
Value: 2.0E-6
Constant
 
 kactDUBp53
Value: 1.0E-7
Constant
 
 kactDUBProtp53
Value: 1.0E-4
Constant
 
 kactDUBMdm2
Value: 1.0E-7
Constant
 
 kMdm2Ub
Value: 4.56E-6
Constant
 
 kMdm2PUb
Value: 6.84E-6
Constant
 
 kMdm2PolyUb
Value: 0.00456
Constant
 
 kdam
Value: 0.08
Constant
 
 krepair
Value: 2.0E-5
Constant
 
 kactATM
Value: 1.0E-4
Constant
 
 kinactATM
Value: 5.0E-4
Constant
 
 kphosp53
Value: 2.0E-4
Constant
 
 kdephosp53
Value: 0.5
Constant
 
 kphosMdm2
Value: 2.0
Constant
 
 kdephosMdm2
Value: 0.5
Constant
 
 kphosMdm2GSK3b
Value: 0.005
Constant
 
 kphosMdm2GSK3bp53
Value: 0.5
Constant
 
 kphospTauGSK3bp53
Value: 0.1
Constant
 
 kphospTauGSK3b
Value: 2.0E-4
Constant
 
 kdephospTau
Value: 0.01
Constant
 
 kbinMTTau
Value: 0.1
Constant
 
 krelMTTau
Value: 1.0E-4
Constant
 
 ksynTau
Value: 8.0E-5
Constant
 
 kbinTauProt
Value: 1.925E-7
Constant
 
 kdegTau20SProt
Value: 0.01
Constant
 
 kaggTau
Value: 1.0E-8
Constant
 
 kaggTauP1
Value: 1.0E-8
Constant
 
 kaggTauP2
Value: 1.0E-7
Constant
 
 ktangfor
Value: 0.001
Constant
 
 kprodAbeta
Value: 5.0E-5
Constant
 
 kinhibprot
Value: 1.0E-5
Constant
 
 kdegAbeta
Value: 1.0E-4
Constant
 
 kaggAbeta
Value: 1.0E-8
Constant
 
 kpf
Value: 0.001
Constant
 
 ksynp53mRNAAbeta
Value: 1.0E-5
Constant
 
 kdamROS
Value: 1.0E-5
Constant
 
 kdamBasalROS
Value: 1.0E-9
Constant
 
 kgenROSAbeta
Value: 1.0E-5
Constant
 
 kproteff
Value: 1.0
 
   tot_mdm2
Value: NaN
 
   tot_p53
Value: NaN
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000286

Curator's comment: (updated: 13 Dec 2010 11:39:31 GMT)

The model was integrated using Copasi v4.6 (Build 32). The Stochastic simulation run using Stochastic (Gribson & Bruck) method. The model reproduces figures corresponding to figure 4 of the paper.

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