A Model for How Signal Duration Can Determine Distinct Outcomes of Gene Transcription Programs

DSpace/Manakin Repository

A Model for How Signal Duration Can Determine Distinct Outcomes of Gene Transcription Programs

Citable link to this page

 

 
Title: A Model for How Signal Duration Can Determine Distinct Outcomes of Gene Transcription Programs
Author: Fowler, Kevin D.; Chakraborty, Arup K.; Kuchroo, Vijay Kumar

Note: Order does not necessarily reflect citation order of authors.

Citation: Fowler, Kevin D., Vijay K. Kuchroo, and Arup K. Chakraborty. 2012. A model for how signal duration can determine distinct outcomes of gene transcription programs. PLoS ONE 7(3): e33018.
Full Text & Related Files:
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.
Published Version: doi:10.1371/journal.pone.0033018
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3302786/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10318198
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters