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Achieving Stability of Lipopolysaccharide-Induced NF-κB Activation

Covert, Markus W. and Leung, Thomas H. and Gaston, Jahlionais E. and Baltimore, David (2005) Achieving Stability of Lipopolysaccharide-Induced NF-κB Activation. Science, 309 (5742). pp. 1854-1857. ISSN 0036-8075. doi:10.1126/science.1112304.

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The activation dynamics of the transcription factor NF-κB exhibit damped oscillatory behavior when cells are stimulated by tumor necrosis factor–α (TNFα) but stable behavior when stimulated by lipopolysaccharide (LPS). LPS binding to Toll-like receptor 4 (TLR4) causes activation of NF-κB that requires two downstream pathways, each of which when isolated exhibits damped oscillatory behavior. Computational modeling of the two TLR4-dependent signaling pathways suggests that one pathway requires a time delay to establish early anti-phase activation of NF-κB by the two pathways. The MyD88-independent pathway required Inferon regulatory factor 3–dependent expression of TNFα to activate NF-κB, and the time required for TNFα synthesis established the delay.

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URLURL TypeDescription Online Material
Baltimore, David0000-0001-8723-8190
Additional Information:© 2005 American Association for the Advancement of Science. Received 15 March 2005; accepted 28 July 2005. We thank M. Yamamoto and S. Akira for generously providing the MEFs; M. Boldin, M. Meffert, and A. Hoffmann for valuable discussions; and the Millard and Muriel Jacobs Genetics and Genomics Laboratory at the California Institute of Technology for assistance with the gene expression study. This work was funded by the NIH (GM039458-21). M.W.C. is a Robert Black Fellow supported by the Damon Runyon Cancer Research Foundation (DRG-#1835- 04). T.H.L. is a student in the UCLA–California Institute of Technology Medical Scientist Training Program and supported by the Achievement Rewards for College Scientists foundation.
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Damon Runyon Cancer Research Foundation1835-04
College Scientists FoundationUNSPECIFIED
Issue or Number:5742
Record Number:CaltechAUTHORS:20141117-143614166
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:51865
Deposited By: Tony Diaz
Deposited On:18 Nov 2014 18:15
Last Modified:10 Nov 2021 19:16

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