The Library
Temperature regulates NF-κB dynamics and function through timing of A20 transcription
Tools
Harper, Claire V., Woodcock, Dan J., Lam, Connie, Garcia-Albornoz, Manuel, Adamson, Antony, Ashall, Louise, Rowe, William, Downton, Polly J., Schmidt, Lorraine, West, Simon, Spiller, David G., Rand, David A. and White, Michael R. H. (2018) Temperature regulates NF-κB dynamics and function through timing of A20 transcription. Proceedings of the National Academy of Sciences of the United States of America, 115 (22). E5243-E5249. doi:10.1073/pnas.1803609115 ISSN 1091-6490.
|
PDF
WRAP-temperature-regulates-NF-κB-dynamics-function-through-timing-A20-transcription-Rand-2018.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution Non-commercial No Derivatives 4.0. Download (2164Kb) | Preview |
|
PDF
Rand PNAS 4-18.pdf - Accepted Version Embargoed item. Restricted access to Repository staff only - Requires a PDF viewer. Download (1582Kb) |
||
PDF
PNAS_SI_updated.pdf - Supplemental Material Embargoed item. Restricted access to Repository staff only - Requires a PDF viewer. Download (3777Kb) |
Official URL: https://doi.org/10.1073/pnas.1803609115
Abstract
NF-κB signaling plays a pivotal role in control of the inflammatory response. We investigated how the dynamics and function of NF-κB were affected by temperature within the mammalian physiological range (34 °C to 40 °C). An increase in temperature led to an increase in NF-κB nuclear/cytoplasmic oscillation frequency following Tumor Necrosis Factor alpha (TNFα) stimulation. Mathematical modeling suggested that this temperature sensitivity might be due to an A20-dependent mechanism, and A20 silencing removed the sensitivity to increased temperature. The timing of the early response of a key set of NF-κB target genes showed strong temperature dependence. The cytokine-induced expression of many (but not all) later genes was insensitive to temperature change (suggesting that they might be functionally temperature-compensated). Moreover, a set of temperature- and TNFα-regulated genes were implicated in NF-κB cross-talk with key cell-fate–controlling pathways. In conclusion, NF-κB dynamics and target gene expression are modulated by temperature and can accurately transmit multidimensional information to control inflammation.
Item Type: | Journal Article | ||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Subjects: | Q Science > QH Natural history > QH426 Genetics R Medicine > RB Pathology |
||||||||||||||||||||||||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Mathematics | ||||||||||||||||||||||||||||||
Library of Congress Subject Headings (LCSH): | Inflammation -- Mathematical mdoels, Gene expression | ||||||||||||||||||||||||||||||
Journal or Publication Title: | Proceedings of the National Academy of Sciences of the United States of America | ||||||||||||||||||||||||||||||
Publisher: | National Academy of Sciences | ||||||||||||||||||||||||||||||
ISSN: | 1091-6490 | ||||||||||||||||||||||||||||||
Official Date: | 29 May 2018 | ||||||||||||||||||||||||||||||
Dates: |
|
||||||||||||||||||||||||||||||
Volume: | 115 | ||||||||||||||||||||||||||||||
Number: | 22 | ||||||||||||||||||||||||||||||
Page Range: | E5243-E5249 | ||||||||||||||||||||||||||||||
DOI: | 10.1073/pnas.1803609115 | ||||||||||||||||||||||||||||||
Status: | Peer Reviewed | ||||||||||||||||||||||||||||||
Publication Status: | Published | ||||||||||||||||||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||||||||||||||||||||||||
Date of first compliant deposit: | 2 May 2018 | ||||||||||||||||||||||||||||||
Date of first compliant Open Access: | 31 May 2018 | ||||||||||||||||||||||||||||||
RIOXX Funder/Project Grant: |
|
||||||||||||||||||||||||||||||
Related URLs: |
Request changes or add full text files to a record
Repository staff actions (login required)
View Item |
Downloads
Downloads per month over past year