| First Author | Hoffmann A | Year | 2002 |
| Journal | Science | Volume | 298 |
| Issue | 5596 | Pages | 1241-5 |
| PubMed ID | 12424381 | Mgi Jnum | J:80039 |
| Mgi Id | MGI:2429449 | Doi | 10.1126/science.1071914 |
| Citation | Hoffmann A, et al. (2002) The IkappaB-NF-kappaB signaling module: temporal control and selective gene activation. Science 298(5596):1241-5 |
| abstractText | Nuclear localization of the transcriptional activator NF-kappaB (nuclear factor kappaB) is controlled in mammalian cells by three isoforms of NF-kappaB inhibitor protein: IkappaBalpha, -beta, and - epsilon. Based on simplifying reductions of the IkappaB-NF-kappaB signaling module in knockout cell lines, we present a computational model that describes the temporal control of NF-kappaB activation by the coordinated degradation and synthesis of IkappaB proteins. The model demonstrates that IkappaBalpha is responsible for strong negative feedback that allows for a fast turn-off of the NF-kappaB response, whereas IkappaBbeta and - epsilon function to reduce the system's oscillatory potential and stabilize NF-kappaB responses during longer stimulations. Bimodal signal-processing characteristics with respect to stimulus duration are revealed by the model and are shown to generate specificity in gene expression. |
