A Model for How Signal Duration Can Determine Distinct Outcomes of Gene Transcription Programs
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Fowler-2012-A model for how sign.pdf
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Author(s)
Fowler, Kevin Daniel
Kuchroo, Vijay K.
Chakraborty, Arup K.
Date Issued
March 2012
Journal
PLoS ONE
Publisher
Public Library of Science
Citation
Fowler, Kevin D., Vijay K. Kuchroo, and Arup K. Chakraborty. “A Model for How Signal Duration Can Determine Distinct Outcomes of Gene Transcription Programs.” Ed. Laurel L. Lenz. PLoS ONE 7.3 (2012): e33018.
Version
Final published version
Abstract
The reason why IL-6 induces a pro-inflammatory response, while IL-10 induces an anti-inflammatory response, despite both cytokines activating the same transcription factor, STAT3, is not well understood. It is known that IL-6 induces a transient STAT3 signal and that IL-10 induces a sustained STAT3 signal due to the STAT3-induced inhibitor SOCS3's ability to bind to the IL-6R and not the IL-10R. We sought to develop a general transcriptional network that is capable of translating sustained signals into one response, while translating transient signals into a second response. The general structure of such a network is that the transcription factor STAT3 can induce both an inflammatory response and an anti-inflammatory response by inducing two different genes. The anti-inflammatory gene can bind to and inhibit the inflammatory gene's production and the inflammatory gene can bind to its own promoter and induce its own transcription in the absence of the signal. One prediction that can be made from such a network is that in SOCS3−/− mice, where IL-6 induces a sustained STAT3 signal, that IL-6 would act as an anti-inflammatory cytokine, which has indeed been observed experimentally in the literature.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
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DOI of Published Version
https://doi.org/10.1371/journal.pone.0033018
