Document Detail

Dimer composition and promoter context contribute to functional cooperation between AP-1 and NFAT.
MedLine Citation:
PMID:  17588603     Owner:  NLM     Status:  MEDLINE    
The transcription factors activator protein 1 (AP-1) and nuclear factor of activated T-cells (NFAT) cooperate to induce the expression of cytokines during the immune response. While much is known about the signaling pathways and physical interactions between NFAT and AP-1 dimers following lymphocyte activation, few studies have addressed the role of AP-1 composition in modulating NFAT:AP-1-dependent transcription. We examined the function of specific AP-1 complexes using "tethered" AP-1 dimers with defined composition. We found that NFAT can functionally cooperate with all AP-1 dimers tested. Noteworthy, Jun approximately Jun-containing dimers, which are relatively inactive when tested on an AP-1-dependent promoter, are effective co-activators of an NFAT:AP-1-dependent promoter. Interestingly, specific AP-1 dimer combinations behave differently when tested on interleukin 2 (IL2) and interleukin 4 (IL4) gene regulatory regions. Moreover, the requirement for NFAT to activate each of the promoters is different. Our results suggest that higher NFAT levels are necessary to activate the IL4 promoter. Hence changes in AP-1 composition and the level of participating NFAT proteins can differentially influence cytokine gene expression, resulting in biological consequences for the modulation and dynamics of the immune response.
Marta B Wisniewska; Maya Ameyar-Zazoua; Latifa Bakiri; Bozena Kaminska; Moshe Yaniv; Jonathan B Weitzman
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-06-02
Journal Detail:
Title:  Journal of molecular biology     Volume:  371     ISSN:  0022-2836     ISO Abbreviation:  J. Mol. Biol.     Publication Date:  2007 Aug 
Date Detail:
Created Date:  2007-07-30     Completed Date:  2007-09-27     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2985088R     Medline TA:  J Mol Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  569-76     Citation Subset:  IM    
Pasteur Institute, 25/28 rue du Docteur Roux, 75724 Paris, France.
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MeSH Terms
Interleukin-2 / genetics
Interleukin-4 / genetics
Jurkat Cells
Lymphocyte Activation
NFATC Transcription Factors / metabolism*
Promoter Regions, Genetic / genetics*
Protein Binding
Proto-Oncogene Proteins c-fos / metabolism
Proto-Oncogene Proteins c-jun / metabolism
Transcription Factor AP-1 / metabolism*
Transcription, Genetic
Reg. No./Substance:
0/Interleukin-2; 0/NFATC Transcription Factors; 0/Proto-Oncogene Proteins c-fos; 0/Proto-Oncogene Proteins c-jun; 0/Transcription Factor AP-1; 207137-56-2/Interleukin-4

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