Molecular stripping, targets and decoys as modulators of oscillations in the NF-kB/IkBa/DNA genetic network. Wolynes, P., G., Wang, Z., & Potoyan, D., A. ![Molecular stripping, targets and decoys as modulators of oscillations in the NF-kB/IkBa/DNA genetic network [pdf]](https://bibbase.org/img/filetypes/pdf.svg "pdf")
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Website abstract bibtex DAP, 0000-0002-5860-1699 Eukaryotic transcription factors in the NF-kB 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 IkBa, numerous downstream functional tar-gets, and still more numerous binding sites that do not appear to be directly functional. Under steady stimulation, the regulatory network of NF-kB becomes oscillatory, and temporal patterns of NF-kB 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 gen-eral issue in systems biology. Recently, in vitro kinetic experiments as well as molecular simulations suggest that active stripping of NF-kB by IkBa from its binding sites can modify the traditional systems biology view of NF-kB/IkBa gene circuits. In this work, we revise the commonly adopted minimal model of the NF-kB regulatory network to account for the presence of the large number of binding sites for NF-kB along with dissociation from these sites that may proceed either by passive unbinding or by active molecular strip-ping. We identify regimes where the kinetics of target and decoy unbinding and molecular stripping enter a dynamic tug of war that may either compen-sate each other or amplify nuclear NF-kB activity, leading to distinct oscillatory patterns. Our finding that decoys and stripping play a key role in shaping the NF-kB oscillations suggests strategies to control NF-kB responses by introducing artificial decoys therapeutically.
@article{
title = {Molecular stripping, targets and decoys as modulators of oscillations in the NF-kB/IkBa/DNA genetic network},
type = {article},
keywords = {Life Sciences – Physics interface Subject Areas,NF-kB,Subject Category,genetic oscillations,molecular stripping,synthetic biology,synthetic biology Keywords,systems biology},
websites = {http://dx.doi.org/10.1098/rsif.2016.0606,https://dx.doi.org/10.6084/m9.figshare.c.},
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last_modified = {2017-04-01T18:39:35.606Z},
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abstract = {DAP, 0000-0002-5860-1699 Eukaryotic transcription factors in the NF-kB 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 IkBa, numerous downstream functional tar-gets, and still more numerous binding sites that do not appear to be directly functional. Under steady stimulation, the regulatory network of NF-kB becomes oscillatory, and temporal patterns of NF-kB 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 gen-eral issue in systems biology. Recently, in vitro kinetic experiments as well as molecular simulations suggest that active stripping of NF-kB by IkBa from its binding sites can modify the traditional systems biology view of NF-kB/IkBa gene circuits. In this work, we revise the commonly adopted minimal model of the NF-kB regulatory network to account for the presence of the large number of binding sites for NF-kB along with dissociation from these sites that may proceed either by passive unbinding or by active molecular strip-ping. We identify regimes where the kinetics of target and decoy unbinding and molecular stripping enter a dynamic tug of war that may either compen-sate each other or amplify nuclear NF-kB activity, leading to distinct oscillatory patterns. Our finding that decoys and stripping play a key role in shaping the NF-kB oscillations suggests strategies to control NF-kB responses by introducing artificial decoys therapeutically.},
bibtype = {article},
author = {Wolynes, Peter G and Wang, Zhipeng and Potoyan, Davit A}
}
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