Oscillations in NF-κB Signaling Control the Dynamics of Gene Expression

作者：David E. Nelson, Adaoha Ihekwaba, Malcolm Charles Elliott, James R. Johnson, Gibney Ca, Bo Foreman, Glyn Nelson, Violaine Sée, Caroline A. Horton, David G. Spiller, Steven W. Edwards, Heather P. McDowell, John F. Unitt, Elaine Sullivan, Rachel L. Grimley, Neil Benson, D.S. Broomhead, Douglas Bruce Kell, Michael White · 发表于：Science · 年份：2004 · DOI：10.1126/science.1099962 · 被引用次数：1227 · 研究领域：NF-κB Signaling Pathways、Pharmacological Effects of Natural Compounds、Immune Response and Inflammation

Signaling by the transcription factor nuclear factor kappa B (NF-kappaB) involves its release from inhibitor kappa B (IkappaB) in the cytosol, followed by translocation into the nucleus. NF-kappaB regulation of IkappaBalpha transcription represents a delayed negative feedback loop that drives oscillations in NF-kappaB translocation. Single-cell time-lapse imaging and computational modeling of NF-kappaB (RelA) localization showed asynchronous oscillations following cell stimulation that decreased in frequency with increased IkappaBalpha transcription. Transcription of target genes depended on oscillation persistence, involving cycles of RelA phosphorylation and dephosphorylation. The functional consequences of NF-kappaB signaling may thus depend on number, period, and amplitude of oscillations.