Lipniacki2004 - Mathematical model of NFKB regulatory module

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Short description
its a mathematical model studying impact of TNF on NFKB nuclear dynamics. This model is derived from Hoffmann2002 (PMID:12424381).
Related Publication
  • Mathematical model of NF-kappaB regulatory module.
  • Lipniacki T, Paszek P, Brasier AR, Luxon B, Kimmel M
  • Journal of theoretical biology , 5/ 2004 , Volume 228 , Issue 2 , pages: 195-215 , PubMed ID: 15094015
  • Institute of Fundamental Technological Research, Warsaw, Poland.
  • The two-feedback-loop regulatory module of nuclear factor kappaB (NF-kappaB) signaling pathway is modeled by means of ordinary differential equations. The constructed model involves two-compartment kinetics of the activators IkappaB (IKK) and NF-kappaB, the inhibitors A20 and IkappaBalpha, and their complexes. In resting cells, the unphosphorylated IkappaBalpha binds to NF-kappaB and sequesters it in an inactive form in the cytoplasm. In response to extracellular signals such as tumor necrosis factor or interleukin-1, IKK is transformed from its neutral form (IKKn) into its active form (IKKa), a form capable of phosphorylating IkappaBalpha, leading to IkappaBalpha degradation. Degradation of IkappaBalpha releases the main activator NF-kappaB, which then enters the nucleus and triggers transcription of the inhibitors and numerous other genes. The newly synthesized IkappaBalpha leads NF-kappaB out of the nucleus and sequesters it in the cytoplasm, while A20 inhibits IKK converting IKKa into the inactive form (IKKi), a form different from IKKn, no longer capable of phosphorylating IkappaBalpha. After parameter fitting, the proposed model is able to properly reproduce time behavior of all variables for which the data are available: NF-kappaB, cytoplasmic IkappaBalpha, A20 and IkappaBalpha mRNA transcripts, IKK and IKK catalytic activity in both wild-type and A20-deficient cells. The model allows detailed analysis of kinetics of the involved proteins and their complexes and gives the predictions of the possible responses of whole kinetics to the change in the level of a given activator or inhibitor.
Submitter of the first revision: Krishna Kumar Tiwari
Submitter of this revision: Krishna Kumar Tiwari
Modellers: Krishna Kumar Tiwari

Metadata information

is (2 statements)
BioModels Database BIOMD0000000786
BioModels Database MODEL1908090003

isDescribedBy (1 statement)
PubMed 15094015

hasTaxon (1 statement)
Taxonomy Mus musculus

hasProperty (3 statements)
isPartOf (1 statement)
occursIn (1 statement)

Curation status


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Model files

Lipniacki2004.xml SBML L2V4 representation of Lipniacki2004 model 233.26 KB Preview | Download

Additional files

Lipniacki2004.cps COPASI 4.24 (build 197) file for Lipniacki2004 model 234.71 KB Preview | Download
Lipniacki2004.sedml SEDML file for Lipniacki2004 model 3.72 KB Preview | Download

  • Model originally submitted by : Krishna Kumar Tiwari
  • Submitted: Aug 9, 2019 5:06:41 PM
  • Last Modified: Aug 9, 2019 5:06:41 PM
  • Version: 2 public model Download this version
    • Submitted on: Aug 9, 2019 5:06:41 PM
    • Submitted by: Krishna Kumar Tiwari
    • With comment: Automatically added model identifier BIOMD0000000786
: Variable used inside SBML models

Reactions Rate Parameters
IKK_active => IKK_inact Cytosol*k3*IKK_active k3 = 0.0015
IkB_NFKB => NFKB Cytosol*c6a*IkB_NFKB c6a = 2.0E-5
NFKB_nuc + IkB_nuc => IkB_NFKB_nuc Nucleus*a1*NFKB_nuc*IkB_nuc a1 = 0.5
IkB_nuc => Nucleus*function_for_transport(e1a, Kv, IkB_nuc) Kv = 5.0; e1a = 5.0E-4
IkB_NFKB_nuc => Nucleus*function_for_transport(e2a, Kv, IkB_NFKB_nuc) Kv = 5.0; e2a = 0.01
IKKactive_IkB_NFKB => IKK_active + NFKB Cytosol*t2*IKKactive_IkB_NFKB t2 = 0.1
IKK_active => IKK_inact; TNF, A20 Cytosol*function_for_R26(k2, TNF, A20, IKK_active) k2 = 0.1
NFKB + IkB => IkB_NFKB Cytosol*a1*NFKB*IkB a1 = 0.5
IKK_active + IkB_NFKB => IKKactive_IkB_NFKB Cytosol*a3*IKK_active*IkB_NFKB a3 = 1.0
=> A20; A20_mRNA function_for_substrateless_production(c4, A20_mRNA) c4 = 0.5
Curator's comment:
(added: 09 Aug 2019, 17:05:47, updated: 09 Aug 2019, 17:05:47)
Model is created and data generated using COPASI 4,24 (build 197). Model is pre-simulated for 101 hours (363600 seconds) before triggering the system with TNF. Model is simulated for 6 hours post TNF stimulation (385200 seconds). Data presented include last 1 hours of pre-TNF stimulation + 6 hours of post TNF stimulation. Attached Copasi file will reproduce literature figure 3b, 3h, 3i, 3j by default. Data plotted using Microsoft excel.