Transcriptional Complexes Formed by NFAT Dimers Regulate the Induction of T Cell Tolerance

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Transcriptional Complexes Formed by NFAT Dimers Regulate the Induction of T Cell Tolerance

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dc.contributor.author Soto-Nieves, Noemi
dc.contributor.author Puga, Irene
dc.contributor.author Abe, Brian T.
dc.contributor.author Bandyopadhyay, Sanmay
dc.contributor.author Baine, Ian
dc.contributor.author Macian, Fernando
dc.contributor.author Rao, Anjana
dc.date.accessioned 2010-11-08T17:23:30Z
dc.date.issued 2009
dc.identifier.citation Soto-Nieves, Noemi, Irene Puga, Brian T. Abe, Sanmay Bandyopadhyay, Ian Baine, Anjana Rao, and Fernando Macian. 2009. Transcriptional complexes formed by NFAT dimers regulate the induction of T cell tolerance. The Journal of Experimental Medicine 206(4): 867-876. en_US
dc.identifier.issn 0022-1007 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:4551467
dc.description.abstract In T cells, anergy can be induced after T cell receptor engagement in the absence of costimulation. Under these conditions, the expression of a specific set of anergy-associated genes is activated. Several lines of evidence suggest that nuclear factor of activated T cells (NFAT) proteins may regulate the expression of many of those genes; however, the nature of the complexes responsible for the induction of this new program of gene expression is unknown. Here, we show that transcriptional complexes formed by NFAT homodimers are directly responsible for the activation of at least two anergy-inducing genes, Grail and Caspase3. Our data shows that Grail expression is activated by direct binding of NFAT dimers to the Grail promoter at two different sites. Consequently, a mutant NFAT protein with impaired ability to dimerize is not able to induce an unresponsive state in T cells. Our results not only identify a new biological function for NFAT dimers but also reveal the different nature of NFAT-containing complexes that induce anergy versus those that are activated during a productive immune response. These data also establish a basis for the design of immunomodulatory strategies that specifically target each type of complex. en_US
dc.description.sponsorship Molecular and Cellular Biology en_US
dc.language.iso en_US en_US
dc.publisher The Rockefeller University Press en_US
dc.relation.isversionof doi:10.1084/jem.20082731 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2715123/pdf/ en_US
dash.license LAA
dc.title Transcriptional Complexes Formed by NFAT Dimers Regulate the Induction of T Cell Tolerance en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal The Journal of Experimental Medicine en_US
dash.depositing.author Rao, Anjana
dc.date.available 2010-11-08T17:23:30Z

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  • FAS Scholarly Articles [6466]
    Peer reviewed scholarly articles from the Faculty of Arts and Sciences of Harvard University

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