BIOMD0000000252
type: SBMLModel
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is version of: GO:0006950
is part of: map04115
creator:
  ORG:
    orgname: Niels Bohr Institute
  n:
    given: Alexander
    family: Hunziker
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curated: true
units def: metaid_0000004
is: MODEL1006280000
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  W3 CDTF: Fri Nov 30 16:42:32 GMT 2012
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creator:
  ORG:
    orgname: EMBL-EBI
  n:
    given: Vijayalakshmi
    family: Chelliah
parameter: metaid_0000006
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created:
  W3 CDTF: Fri Jul 16 14:06:03 BST 2010
species: metaid_0000017
notes: This a model from the article: Stress-specific response of the p53-Mdm2 feedback loop Alexander Hunziker, Mogens H Jensen and Sandeep Krishna BMC Systems Biology 2010, Jul 12;4(1):94 20624280 , Abstract: ABSTRACT: BACKGROUND: The p53 signalling pathway has hundreds of inputs and outputs. It can trigger cellular senescence, cell-cycle arrest and apoptosis in response to diverse stress conditions, including DNA damage, hypoxia and nutrient deprivation. Signals from all these inputs are channeled through a single node, the transcription factor p53. Yet, the pathway is flexible enough to produce different downstream gene expression patterns in response to different stresses. RESULTS: We construct a mathematical model of the negative feedback loop involving p53 and its inhibitor, Mdm2, at the core of this pathway, and use it to examine the effect of different stresses that trigger p53. In response to DNA damage, hypoxia, etc., the model exhibits a wide variety of specific output behaviour -- steady states with low or high levels of p53 and Mdm2, as well as spiky oscillations with low or high average p53 levels. CONCLUSIONS: We show that even a simple negative feedback loop is capable of exhibiting the kind of flexible stress-specific response observed in the p53 system. Further, our model provides a framework for predicting the differences in p53 response to different stresses and single nucleotide polymorphisms. The parameters of the model corresponds to the resting state, with delta = 11hr -1 , gamma = 0.2hr -1 , k t = 0.03nM -1 hr -1 and k f = 5000nM -1 hr -1 . To simulate different stress conditions as in figure 2A (also look at the curation figure of this model) of the reference publication, the above parameter should be changed. The parameter values corresponding to different stress conditions are shown in the following table. Stress Condition/Parameter delta gamma k t k f Nutlin 11hr -1 0.2hr -1 0.03nM -1 hr -1 500nM -1 hr -1 Oncogene 2hr -1 0.2hr -1 0.03nM -1 hr …
name: Hunziker2010_p53_StressSpecificResponse
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units def: metaid_0000005
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is described by: http://identifiers.org/pubmed/20624280
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parameter: metaid_0000009
compartment: metaid_0000015
has part: GO:0001666
is part of: REACT 309
length unit: length
area units: metaid_0000005
species: metaid_0000019
occurs in: http://identifiers.org/taxonomy/2759
time units: metaid_0000004

metaid_0000008
type: Parameter
notes: For the stress condition Hypoxia, the value should be changed to 0.01. For the rest of the stress conditions the value remains the same.
is: SBO:0000009
constant: true
value: 0.03
name: k_t

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metaid_0000016
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spatial dimensions: 3.0
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metaid_0000012
type: Parameter
is: SBO:0000356
constant: true
value: 0.6
name: beta

metaid_0000011
type: Parameter
notes: For the stress conditions Nutlin and DNA damage, the values should be changed to 500 and 2500 respectively. For the rest of the stress conditions, the value remains the same.
is: SBO:0000337
constant: true
value: 5000.0
name: k_f

metaid_0000007
type: Parameter
is: SBO:0000356
constant: true
value: 0.1
name: alpha

metaid_0000006
type: Parameter
constant: true
value: 1000.0
name: S

metaid_0000017
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name: mm
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initial amount: NaN
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name: m
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metaid_0000010
type: Parameter
is: SBO:0000282
constant: true
value: 7200.0
name: k_b

metaid_0000014
type: Parameter
notes: For the stress conditions DNA damage, Oncogene and Hypoxia, the value should be changed to 2. For Nutlin the value remains the same.
is: SBO:0000356
constant: true
value: 11.0
name: delta

metaid_0000013
type: Parameter
notes: For the stress condition DNA damage, the values should be changed to 0.5. For the rest of the stress conditions the value remains the same.
is: SBO:0000356
constant: true
value: 0.2
name: gamma

metaid_0000009
type: Parameter
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value: 1.4
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