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BIOMD0000000420 - Ratushny2012_ASSURE_I

 

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Reference Publication
Publication ID: 22531117
Ratushny AV, Saleem RA, Sitko K, Ramsey SA, Aitchison JD.
Asymmetric positive feedback loops reliably control biological responses.
Mol. Syst. Biol. 2012; 8: 577
Institute for Systems Biology, Seattle, WA, USA.  [more]
Model
Original Model: Ratushny2012_ASSURE_I
Submitter: Alexander Ratushny
Submission ID: MODEL1203010001
Submission Date: 01 Mar 2012 00:56:48 UTC
Last Modification Date: 11 Jul 2012 18:15:28 UTC
Creation Date: 10 May 2012 17:52:59 UTC
Encoders:  Vijayalakshmi Chelliah
   Alexander Ratushny
set #1
bqbiol:isVersionOf Gene Ontology regulation of transcription, DNA-templated
set #2
bqbiol:occursIn Taxonomy Saccharomyces cerevisiae
Notes

This model is from the article:
Asymmetric positive feedback loops reliably control biological responses
Alexander V Ratushny, Ramsey A Saleem, Katherine Sitko, Stephen A Ramsey & John D Aitchison Mol Syst Biol. 2012 Apr 24;8:577. 22531117 ,
Abstract:
Positive feedback is a common mechanism enabling biological systems to respond to stimuli in a switch-like manner. Such systems are often characterized by the requisite formation of a heterodimer where only one of the pair is subject to feedback. This ASymmetric Self-UpREgulation (ASSURE) motif is central to many biological systems, including cholesterol homeostasis (LXRα/RXRα), adipocyte differentiation (PPARγ/RXRα), development and differentiation (RAR/RXR), myogenesis (MyoD/E12) and cellular antiviral defense (IRF3/IRF7). To understand why this motif is so prevalent, we examined its properties in an evolutionarily conserved transcriptional regulatory network in yeast (Oaf1p/Pip2p). We demonstrate that the asymmetry in positive feedback confers a competitive advantage and allows the system to robustly increase its responsiveness while precisely tuning the response to a consistent level in the presence of varying stimuli. This study reveals evolutionary advantages for the ASSURE motif, and mechanisms for control, that are relevant to pharmacologic intervention and synthetic biology applications.


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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: 22531117 Submission Date: 01 Mar 2012 00:56:48 UTC Last Modification Date: 11 Jul 2012 18:15:28 UTC Creation Date: 10 May 2012 17:52:59 UTC
Mathematical expressions
Reactions
___r1 ___r2 ___r3 ___r4
Rules
Assignment Rule (variable: dsp1ksp) Assignment Rule (variable: dsp1p2kd)    
Physical entities
Compartments Species
univ P2 Target  
Global parameters
Kd Ksp P1 dsp1ksp
dsp1p2kd h k0 ka
ks ku s  
Reactions (4)
 
 ___r1  → [P2];  
 
 ___r2 [P2] → ;  
 
 ___r3  → [Target];  
 
 ___r4 [Target] → ;  
 
Rules (2)
 
 Assignment Rule (name: dsp1ksp) dsp1ksp = Ksp/2*(1+(s+P1)/Ksp-((1+(s+P1)/Ksp)^2-4*s*P1/Ksp^2)^0.5)
 
 Assignment Rule (name: dsp1p2kd) dsp1p2kd = Kd/2*(1+(dsp1ksp+P2*univ)/Kd-((1+(dsp1ksp+P2*univ)/Kd)^2-4*dsp1ksp*P2*univ/Kd^2)^0.5)
 
  Spatial dimensions: 3.0  Compartment size: 1.0
 
 P2
Compartment: univ
Initial amount: 10.0
 
 Target
Compartment: univ
Initial amount: 10.0
 
Global Parameters (11)
 
   Kd
Value: 1.0E-5
Constant
 
   Ksp
Value: 0.0010
Constant
 
   P1
Value: 40.0
Constant
 
   dsp1ksp
Value: NaN
 
   dsp1p2kd
Value: NaN
 
   h
Value: 2.0
Constant
 
   k0
Value: 0.1
Constant
 
   ka
Value: 40.0
Constant
 
   ks
Value: 10.0
Constant
 
   ku
Value: 0.1
Constant
 
   s
Value: 1000.0
Constant
 
___r2 (1)
 
   __RATE__
Value: 0.1
Constant
 
___r4 (1)
 
   __RATE__
Value: 0.1
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000420

Curator's comment: (updated: 11 May 2012 11:45:57 BST)

The plot corresponding to "ASSURE1" in Figure 2f of the reference publication has been reproduced here. The data for the plot was obtained by simulating the model using Copasi v4.8 (Build 35) and plotted using gnuplot.

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