| Autor: |
O'Dea, Ellen L, Barken, Derren, Peralta, Raechel Q, Tran, Kim T, Werner, Shannon L, Kearns, Jeffrey D, Levchenko, Andre, Hoffmann, Alexander |
| Předmět: |
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| Zdroj: |
Molecular Systems Biology; 2007, Vol. 3 Issue 1, p111-N.PAG, 1p, 1 Black and White Photograph, 1 Chart, 2 Graphs |
| Abstrakt: |
Cellular signal transduction pathways are usually studied following administration of an external stimulus. However, disease-associated aberrant activity of the pathway is often due to misregulation of the equilibrium state. The transcription factor NF-κB is typically described as being held inactive in the cytoplasm by binding its inhibitor, IκB, until an external stimulus triggers IκB degradation through an IκB kinase-dependent degradation pathway. Combining genetic, biochemical, and computational tools, we investigate steady-state regulation of the NF-κB signaling module and its impact on stimulus responsiveness. We present newly measured in vivo degradation rate constants for NF-κB-bound and -unbound IκB proteins that are critical for accurate computational predictions of steady-state IκB protein levels and basal NF-κB activity. Simulations reveal a homeostatic NF-κB signaling module in which differential degradation rates of free and bound pools of IκB represent a novel cross-regulation mechanism that imparts functional robustness to the signaling module. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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