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NF-κB WebModel
ver 3.0 public

Model/Analysis

Results

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NF-kB Model 1.0

Description

  • Recapitulates activation and attenuation of NF-kB in response to TNF pulse (> 5min) and persistent stimulation
  • Was also used in Barken et al. 2005 Science 308, pp.52a: amplitude and period of oscillatory response is regulated by the NF-kB expression level
  • Uses an assumed IKK curve as input (replaced in v2.1.)
  • Includes regulated IkBb transport to mimic nuclear accumulation of a hypo-phosphorylated form reported by S Ghosh lab (removed in v1.2.)
  • Unable to recapitulate NF-kB control in IkB knockouts (fixed in v1.2.)

Paper

Stimulus Specificity of Gene Expression Programs Determined by Temporal Control of IKK Activity

Hoffmann et al. 2002 Science 298 pp.1241 (Link)

NF-kB Model 1.2

Description

  • Recapitulates IkB protein levels and NF-kB activity of "resting" cells in all IkB knockouts tested, as well as TNF-induced timecourses
  • Includes newly measured degradation rate constants of free and bound IkB protein pools, and basal IKK activity (O'Dea et al. 2007, MSB 3:111)
  • Includes newly described negative feedback for IkBe, provides mechanism for steadying NF-kB activity at late times of the TNF timecourse
  • mRNA synthesis parameters fit to actual mRNA profiles of IkBa, IkBb, IkBe

Paper

IkBe provides negative feedback to control NF-kB oscillations, signaling dynamics, and inflammatory gene expression.

Kearns et al. 2006, JCB 173, pp.659 (Link)

NF-kB Model 2.1

Description

  • Recapitulates both TNF and LPS-induced NF-kB signaling up to 2 hrs
  • Utilizes numerically defined IKK activity profiles as inputs for simulations
  • Improved nucleo-cytoplasmic transport parameters
  • Supports a comprehensive parameter sensitivity analysis for TNFc, TNFp and LPSp signaling (Barken et al in prep)

Paper

Stimulus Specificity of Gene Expression Programs Determined by Temporal Control of IKK Activity

Werner/Barken et al 2005, Science 309 pp.1857 (Link)

NF-kB Model 3.0

Description

  • Recapitulates RelA NF-kB activation in response to stimulation of LTbR, TNFR, and TLR4, and crosstalk between TNFR and LTbR signaling
  • Includes a newly characterized 4th IkB activity (multimeric complex of p100) whose degradation is unresponsive to TNF but responsive to LTbR
  • Allows for numerically defined (experimentally measured) inputs for IKK1 and IKK2

Paper

A Fourth IkB Protein within the NF-kB Signaling Module

Basak et al. 2007, Cell 128, pp.369 (Link)