The Library
Signal transduction controls heterogeneous NF-κB dynamics and target gene expression through cytokine-specific refractory states
Tools
Tools
Tools
Adamson, Antony, Boddington, Christopher, Downton, Polly, Rowe, William, Bagnall, James, Lam, Connie, Maya-Mendoza, Apolinar, Schmidt, Lorraine, Harper, Claire V., Spiller, David G., Rand, David A., Jackson, Dean A., White, Michael R. H. and Paszek, Pawel (2016) Signal transduction controls heterogeneous NF-κB dynamics and target gene expression through cytokine-specific refractory states. Nature Communications, 7 . 12057. doi:10.1038/ncomms12057 ISSN 2041-1723.
Research output not available from this repository.
Request-a-Copy directly from author or use local Library Get it For Me service.
Official URL: http://dx.doi.org/10.1038/ncomms12057
Abstract
Cells respond dynamically to pulsatile cytokine stimulation. Here we report that single, or well-spaced pulses of TNFα (>100 min apart) give a high probability of NF-κB activation. However, fewer cells respond to shorter pulse intervals (<100 min) suggesting a heterogeneous refractory state. This refractory state is established in the signal transduction network downstream of TNFR and upstream of IKK, and depends on the level of the NF-κB system negative feedback protein A20. If a second pulse within the refractory phase is IL-1β instead of TNFα, all of the cells respond. This suggests a mechanism by which two cytokines can synergistically activate an inflammatory response. Gene expression analyses show strong correlation between the cellular dynamic response and NF-κB-dependent target gene activation. These data suggest that refractory states in the NF-κB system constitute an inherent design motif of the inflammatory response and we suggest that this may avoid harmful homogenous cellular activation.
| Item Type: | Journal Article | ||||||
|---|---|---|---|---|---|---|---|
| Divisions: | Faculty of Science, Engineering and Medicine > Science > Mathematics Faculty of Science, Engineering and Medicine > Research Centres > Warwick Systems Biology Centre |
||||||
| Journal or Publication Title: | Nature Communications | ||||||
| Publisher: | Nature Publishing Group | ||||||
| ISSN: | 2041-1723 | ||||||
| Official Date: | 2016 | ||||||
| Dates: |
|
||||||
| Volume: | 7 | ||||||
| Article Number: | 12057 | ||||||
| DOI: | 10.1038/ncomms12057 | ||||||
| Status: | Peer Reviewed | ||||||
| Publication Status: | Published | ||||||
| Access rights to Published version: | Open Access (Creative Commons) |
Request changes or add full text files to a record
Repository staff actions (login required)
 |
View Item |
