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The IB-NF-B Signaling Module: Temporal Control and Selective Gene Activation
Alexander Hoffmann,1*Andre Levchenko,2*Martin L. Scott,3David Baltimore1
Nuclear localization of the transcriptional activator
NF-B (nuclear factor B) is controlled in mammalian cells by threeisoforms of NF-B inhibitor protein: IB, -, and
-. Based onsimplifying reductions of the
IB-NF-B signaling module in knockoutcell lines, we
present a computational model that describes thetemporal control of
NF-B activation by the coordinated degradationand synthesis of
IB proteins. The model demonstrates that IBis responsible for
strong negative feedback that allows for afast turn-off of the NF-B
response, whereas IB and - functionto reduce the
system's oscillatory potential and stabilize NF-Bresponses during
longer stimulations. Bimodal signal-processingcharacteristics with
respect to stimulus duration are revealedby the model and are shown to
generate specificity in gene expression.
1 Division of Biology, California Institute of
Technology, Pasadena, CA 91125, USA.
2 Department of
Biomedical Engineering, Johns Hopkins University, Baltimore, MD
21218, USA.
3 Department of Biology, Massachusetts
Institute of Technology, Cambridge, MA 02139, USA.
*
These authors contributed equally to this work.
Present address: Biogen, Incorporated, Cambridge, MA 02142, USA.
To whom correspondence should be addressed. E-mail:
baltimo{at}caltech.edu
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