Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Mol Syst Biol. 2007;3:111. Epub 2007 May 8.

A homeostatic model of IkappaB metabolism to control constitutive NF-kappaB activity.

Author information

  • 1Signaling Systems Laboratory, Department of Chemistry and Biochemistry, UCSD, La Jolla, CA 92037, USA.

Abstract

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-kappaB is typically described as being held inactive in the cytoplasm by binding its inhibitor, IkappaB, until an external stimulus triggers IkappaB degradation through an IkappaB kinase-dependent degradation pathway. Combining genetic, biochemical, and computational tools, we investigate steady-state regulation of the NF-kappaB signaling module and its impact on stimulus responsiveness. We present newly measured in vivo degradation rate constants for NF-kappaB-bound and -unbound IkappaB proteins that are critical for accurate computational predictions of steady-state IkappaB protein levels and basal NF-kappaB activity. Simulations reveal a homeostatic NF-kappaB signaling module in which differential degradation rates of free and bound pools of IkappaB represent a novel cross-regulation mechanism that imparts functional robustness to the signaling module.

PMID:
17486138
[PubMed - indexed for MEDLINE]
PMCID:
PMC2673708
Free PMC Article

Images from this publication.See all images (3)Free text

Figure 1
Figure 2
Figure 3
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk