Lipniacki2004 - Mathematical model of NFKB regulatory module
Model Identifier
BIOMD0000000786
Short description
its a mathematical model studying impact of TNF on NFKB nuclear dynamics. This model is derived from Hoffmann2002 (PMID:12424381).
Format
SBML
(L2V4)
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. tomek@rice.edu
- 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.
Contributors
Submitter of the first revision: Krishna Kumar Tiwari
Submitter of this revision: Krishna Kumar Tiwari
Modellers: Krishna Kumar Tiwari
Submitter of this revision: Krishna Kumar Tiwari
Modellers: Krishna Kumar Tiwari
Metadata information
is (2 statements)
isDescribedBy (1 statement)
hasTaxon (1 statement)
hasProperty (3 statements)
isPartOf (1 statement)
occursIn (1 statement)
isDescribedBy (1 statement)
hasTaxon (1 statement)
hasProperty (3 statements)
Mathematical Modelling Ontology
Ordinary differential equation model
NCIt NFKB Activation Pathway
Gene Ontology response to tumor necrosis factor
NCIt NFKB Activation Pathway
Gene Ontology response to tumor necrosis factor
isPartOf (1 statement)
occursIn (1 statement)
Curation status
Curated
Modelling approach(es)
Tags
Connected external resources
SBGN view in Newt Editor
| Name | Description | Size | Actions |
|---|---|---|---|
Model files |
|||
| Lipniacki2004.xml | SBML L2V4 representation of Lipniacki2004 model | 233.26 KB | Preview | Download |
Additional files |
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| 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
Revisions
-
Version: 2
- Submitted on: Aug 9, 2019 5:06:41 PM
- Submitted by: Krishna Kumar Tiwari
- With comment: Automatically added model identifier BIOMD0000000786
Legends
: Variable used inside SBML models
: Variable used inside SBML models
Species
| Species | Initial Concentration/Amount |
|---|---|
| IKK inact Inhibitor of nuclear factor kappa-B kinase subunit alpha |
0.0 μmol |
| NFKB Nuclear factor NF-kappa-B p105 subunit |
0.0 μmol |
| NFKB nuc Nuclear factor NF-kappa-B p105 subunit |
0.0 μmol |
| IkB nuc NF-kappa-B inhibitor alpha |
0.0 μmol |
| IkB NFKB nuc NF-kappa-B inhibitor alpha ; Nuclear factor NF-kappa-B p105 subunit |
0.0 μmol |
| IKKactive IkB NFKB Nuclear factor NF-kappa-B p105 subunit ; Inhibitor of nuclear factor kappa-B kinase subunit alpha ; NF-kappa-B inhibitor alpha |
0.0 μmol |
| IkB NFKB Nuclear factor NF-kappa-B p105 subunit ; NF-kappa-B inhibitor alpha |
0.06 μmol |
| IKK active Inhibitor of nuclear factor kappa-B kinase subunit alpha |
0.0 μmol |
| A20 Tumor necrosis factor alpha-induced protein 3 |
0.0 μmol |
Reactions
| 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)
(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.