TABLE 1
FROM:
Understanding NF-
B signaling via mathematical modeling
Raymond Cheong, Alexander Hoffmann & Andre Levchenko
doi:10.1038/msb.2008.30
BACK TO ARTICLETable 1: Comparison of published NF-
B models
| Model | Predecessor | Feedback | Major changes from predecessor |
|---|---|---|---|
The original mathematical model of NF- B signaling | |||
| Hoffmann et al (2002) | Carlotti et al (2000) | Inducible I B![]() Constitutive I B , I B![]() | Responsive to IKK stimulus I B negative feedback loop |
| Direct descendants of the original model | |||
| Covert et al (2005) | Hoffmann et al (2002) | Inducible I B![]() Constitutive I B , I B![]() | LPS stimulus modeled as two additive signals offset in time Transcription and translation rates were re-fit |
| O'Dea et al (2007) | Hoffmann et al (2002) | Inducible I B![]() Constitutive I B , I B![]() | I B degradation rates were updated based on experimental measurements |
| Cheong et al (2006) | Hoffmann et al (2002) | Inducible I B ,Constitutive I B , I B![]() | IKK time-course generator was added Transcription, translation, and degradation rates were re-fit Nuclear–cytoplasmic volume ratio was added |
| Kearns et al (2006) | O'Dea et al (2007) | Inducible I B![]() Delayed inducible I B , I B![]() | I B and I B are inducible with a 45 min delay I B degradation rates were altered to fit new data |
| Werner et al (2005) | Kearns et al (2006) | Inducible I B![]() Delayed inducible I B , I B![]() | Cubic transcription rate LPS modeled by using its IKK time course as an input |
| Moss et al (2008) | Identical to the model described in Werner et al (2005) | ||
| O'Dea et al (2008) | Werner et al (2005) | Inducible I B![]() Delayed inducible I B , I B![]() | Some rate parameters were modified to model the effect of UV-induced NF- B activity |
| Mathes et al (2008) | Werner et al (2005) | Inducible I B![]() Delayed inducible I B , I B![]() | Some rate parameters were modified to model the effect of I B mutants on NF- B signaling |
| Basak et al (2007) | Werner et al (2005) | Inducible I B , p100Delayed inducible I B , I B![]() | Introduction of the I B species p100 LPS or TNF induces IKK2-mediated I B degradation LT induces IKK1-mediated p100 degradation |
| Analysis of the original model by MR White and colleagues | |||
| Nelson et al (2004) | Identical to the model described in Hoffmann et al (2002) | ||
| Ihekwaba et al (2004) | Identical to the model described in Hoffmann et al (2002) | ||
| Ihekwaba et al (2005) | Identical to the model described in Hoffmann et al (2002) | ||
| Ihekwaba et al (2007) | Hoffmann et al (2002) | Inducible I B![]() Constitutive I B , I B![]() | Identical to predecessor except some IKK-related parameters changed to match measurements based on experiments where cells were stimulated with IL-1 |
NF- B models by M Kimmel and colleagues | |||
| Lipniacki et al (2004) | Hoffmann et al (2002) | Inducible I B![]() Inducible A20 | I B and I B were removed from predecessor and A20 negative feedback loop was added New assumptions about IKK activation and deactivation Nuclear–cytoplasmic volume ratio was added Transcription and translation rates were re-fit |
| Lipniacki et al (2006) | Lipniacki et al (2004) | Inducible I B![]() Inducible A20 | Stochastic translation and transcription Some parameters were re-fit |
| Lipniacki et al (2007) | Lipniacki et al (2006) | Inducible I B![]() Inducible A20 | Introduction of TNF receptor and IKK kinase Stochastic TNF receptor activation and I B /A20 transcription |
| Fujarewicz et al (2007) | Lipniacki et al (2004) | Inducible I B![]() Inducible A20 | Equations identical to predecessor but parameters were re-fit |
| Joo et al (2007) | Identical to the model described in Lipniacki et al (2004) | ||
| Other descendants of the original model | |||
| Sung and Simon (2004) | Hoffmann et al (2002) | Inducible I B![]() | I B and I B are removed from predecessor NF- B induction of I B has an explicit transcriptional time delay Some parameters were re-fit |
| Hayot and Jayaprakash (2006) | Hoffmann et al (2002) | Inducible I B![]() | I B and I B are removed, and I B has linear transcription rate Whole model is stochastic |
| Krishna et al (2006) | Hoffmann et al (2002) | Inducible I B![]() | Reduces predecessor to a three-component system with five dimensionless parameters |
| Park et al (2006) | Hoffmann et al (2002) | Inducible I B![]() Constitutive I B , I B![]() | Explicit TNF receptor to IKK pathway IKK activity was affected by factors X and Y representing effects of HBV infection |
Other NF- B models | |||
| Cho et al (2003) | None | No inducible factors | Tree-like signaling pathway structure with no feedback loops TNF leads either to apoptosis (FADD) or proliferation (NF- B) |
| Monk (2003) | None | Inducible I B![]() | Proposes NF- B oscillations derive from time delay of I B transcription |
| Janes et al (2005) | None | Partial least-squares regression on a large compendium of cytokine signaling data | |
| Janes et al (2006) | Identical to the model described in Janes et al (2005) | ||
| Piotrowska et al (2006) | None | No inducible factors | Two-component system with five dimensionless parameters Negative correlation between I B and NF- B is directly assumed Proliferation rate is a function of NF- B |
| Pogson et al (2006) | None | No inducible factors | Agent-based stochastic simulation Incorporates events from receptor activation to NF- B nuclear import |
| Rangamani and Sirovich (2007) | None | Inducible I B![]() Inducible IAP | TNF leads either to apoptosis (caspase) or survival (NF- B) I B and I B are not present Parameters were taken from a variety of sources |

B signaling
B
, I
Responsive to IKK stimulus