Molecular stripping, targets and decoys as modulators of oscillations in the NF-κB/IκBα/DNA genetic network

Simple item page
dc.citation.articleNumber20160606
dc.citation.journalTitleJournal of the Royal Society Interfaceen_US
dc.citation.volumeNumber13en_US
dc.contributor.authorWang, Zhipengen_US
dc.contributor.authorPotoyan, Davit A.en_US
dc.contributor.authorWolynes, Peter G.en_US
dc.contributor.orgCenter for Theoretical Biological Physicsen_US
dc.date.accessioned2016-12-01T17:29:09Z
dc.date.available2016-12-01T17:29:09Z
dc.date.issued2016en_US
dc.description.abstractEukaryotic transcription factors in the NF-κB family are central components of an extensive genetic network that activates cellular responses to inflammation and to a host of other external stressors. This network consists of feedback loops that involve the inhibitor IκBα, numerous downstream functional targets, and still more numerous binding sites that do not appear to be directly functional. Under steady stimulation, the regulatory network of NF-κB becomes oscillatory, and temporal patterns of NF-κB pulses appear to govern the patterns of downstream gene expression needed for immune response. Understanding how the information from external stress passes to oscillatory signals and is then ultimately relayed to gene expression is a general issue in systems biology. Recently, in vitro kinetic experiments as well as molecular simulations suggest that active stripping of NF-κB by IκBα from its binding sites can modify the traditional systems biology view of NF-κB/IκBα gene circuits. In this work, we revise the commonly adopted minimal model of the NF-κB regulatory network to account for the presence of the large number of binding sites for NF-κB along with dissociation from these sites that may proceed either by passive unbinding or by active molecular stripping. We identify regimes where the kinetics of target and decoy unbinding and molecular stripping enter a dynamic tug of war that may either compensate each other or amplify nuclear NF-κB activity, leading to distinct oscillatory patterns. Our finding that decoys and stripping play a key role in shaping the NF-κB oscillations suggests strategies to control NF-κB responses by introducing artificial decoys therapeutically.en_US
dc.identifier.citationWang, Zhipeng, Potoyan, Davit A. and Wolynes, Peter G.. "Molecular stripping, targets and decoys as modulators of oscillations in the NF-κB/IκBα/DNA genetic network." <i>Journal of the Royal Society Interface,</i> 13, (2016) The Royal Society: http://dx.doi.org/10.1098/rsif.2016.0606.
dc.identifier.doihttp://dx.doi.org/10.1098/rsif.2016.0606en_US
dc.identifier.urihttps://hdl.handle.net/1911/92730
dc.language.isoengen_US
dc.publisherThe Royal Society
dc.rightsPublished by the Royal Society under the terms of the Creative Commons Attribution Licenseﾠhttp://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleMolecular stripping, targets and decoys as modulators of oscillations in the NF-κB/IκBα/DNA genetic networken_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
20160606.full.pdf
Size:
1.66 MB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Faculty Publications
Chemistry Publications
Physics and Astronomy Publications