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

  title={Oscillations in NF-$\kappa$B Signaling Control the Dynamics of Gene Expression},
  author={D. E. Nelson and Adaoha Elizabeth Ihekwaba and Martin Elliott and James R. Johnson and Claire A Gibney and B. E. Foreman and Glyn Nelson and Violaine S{\'e}e and Caroline A. Horton and David G. Spiller and S. W. Edwards and Heather P. McDowell and John F. Unitt and Elaine Sullivan and Rachel L. Grimley and Neil Benson and David S. Broomhead and Douglas Bruce Kell and Michael R. H. White},
  pages={704 - 708}
Signaling by the transcription factor nuclear factor kappa B (NF-κB) involves its release from inhibitor kappa B (IκB) in the cytosol, followed by translocation into the nucleus. NF-κB regulation of IκBα transcription represents a delayed negative feedback loop that drives oscillations in NF-κB translocation. Single-cell time-lapse imaging and computational modeling of NF-κB (RelA) localization showed asynchronous oscillations following cell stimulation that decreased in frequency with… 
Oscillation dynamics underlie functional switching of NF-κB for B-cell activation
Comprehensive quantitative experiments and mathematical analysis showed that the functional role of switch activation in the NF-κB system is to overcome transient IKK (IκB kinase) activity to amplify nuclear translocation of NF-kkB, thereby inducing the prolonged NF-σB oscillatory behavior necessary for target gene expression and B-cell activation.
Pulsatile Stimulation Determines Timing and Specificity of NF-κB-Dependent Transcription
Altering the stimulation intervals gave different patterns of NF-κB–dependent gene expression, which supports the idea that oscillation frequency has a functional role in nuclear factor κB regulation.
Regulation of signal transduction by spatial parameters: a case in NF-κB oscillation.
regulation mechanisms of NF-κB are described, and the importance of a 'space' for the regulation of oscillation pattern of NF -κB is discussed, showing altered oscillationpattern by the change in spatial parameters such as diffusion coefficient, nuclear to cytoplasmic volume ratio (N/C ratio), and transport through nuclear membrane.
Sustained Oscillations of NF-κB Produce Distinct Genome Scanning and Gene Expression Profiles
It is proposed that negative feedback loops do not simply terminate signaling, but rather promote oscillations of NF-κB in the nucleus, and these oscillations are functionally advantageous.
Regulation of Nuclear NF-κB Oscillation by a Diffusion Coefficient and Its Biological Implications
It is shown that organelle crowding seen in stressed cells possibly changes the oscillation pattern by controlling the effective diffusion coefficient, and altered effective value of diffusion coefficient by diffusion obstacles is shown.
Regulation of NF-κB Oscillation by Nuclear Transport: Mechanisms Determining the Persistency and Frequency of Oscillation
The activated transcription factor NF-κB shuttles between the cytoplasm and the nucleus resulting in the oscillation of nuclear NF-κB (NF-κBn). The oscillation pattern of NF-κBn is implicated in the
Sources of dynamic variability in NF-κB signal transduction: A mechanistic model
It is shown that besides external stimulation intracellular parameters can influence the dynamics of NF-κB and the IκBα transcription rate constant, e.g. by co-factors, provides the possibility of regulating the NF-σ dynamics by crosstalk.
Transcriptional regulation via the NF-κB signaling module
Current understanding of the molecular structures and biochemical mechanisms that determine NF-κB dimer formation and the signal-processing characteristics of the signaling module are summarized and identified as mechanisms that generate specificity in transcriptional regulation.
The Regulation of NF-κB Subunits by Phosphorylation
Importantly, NF-κB phosphorylation controls transcription in a gene-specific manner, offering new opportunities to selectively target NF-σB for therapeutic benefit.
Dynamic Advances in NF-κB Signaling Analysis
An analysis of NF-κB dynamics suggests that the oscillation frequency of NF -κB activation determines which downstream genes are expressed, enabling a single pathway to respond to diverse stimuli in distinct ways.


The IκB-NF-κB Signaling Module: Temporal Control and Selective Gene Activation
A computational model is presented that describes the temporal control of NF-κB activation by the coordinated degradation and synthesis of IκB proteins and demonstrates that IπκBα is responsible for strong negative feedback that allows for a fast turn-off of the NF-σB response.
A cytokine-responsive IκB kinase that activates the transcription factor NF-κB
IKK turns out to be the long-sought-after protein kinase that mediates the critical regulatory step in NF-κB activation, and phosphorylates IκBs on the sites that trigger their degradation.
NF-κB signalling is inhibited by glucocorticoid receptor and STAT6 via distinct mechanisms
Using fluorescent fusion proteins, it is shown that GR alters the timing of activated p65 NF-κB nuclear occupancy by increasing the export rate of p65 and is independent of whether GR is present as a dimer or monomer.
Regulation of distinct biological activities of the NF-κB transcription factor complex by acetylation
Although the proximal cytoplasmic signaling events that control the activation of the NF-κB transcription factor are understood in considerable detail, the subsequent intranuclear events that
Duration of Nuclear NF-κB Action Regulated by Reversible Acetylation
It is demonstrated that the RelA subunit of NF-κB is subject to inducible acetylation and that acetylated forms of RelA interact weakly, if at all, with IκBα.
Differential activation of transcription factors induced by Ca2+ response amplitude and duration
It is reported here that the amplitude and duration of calcium signals in B lymphocytes controls differential activation of the pro–inflammatory transcriptional regulators NF-κB, c-Jun N-terminal kinase (JNK) and NFAT, revealing a mechanism by which a multifunctional second messenger such as Ca2+ can achieve specificity in signalling to the nucleus.
Decoding NF-κB Signaling
A new experiment-driven quantitative model (Hoffmannet al.) seeks to explain how the NF-kB/IkB signaling pathway is fine-tuned so that it can switch on a series of early and late genes in response to a stimulus such as tumor necrosis factor.