Differential Contribution of NFATc2 and NFATc1 to TNF-{alpha} Gene Expression in T Cells.

Differential Contribution of NFATc2 and NFATc1 to TNF-{alpha} Gene Expression in T Cells. Research Abstract Details 

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Differential Contribution of NFATc2 and NFATc1 to TNF-{alpha} Gene Expression in T Cells. Abstract Text:

Osamu Kaminuma,Fujiko Kitamura,Noriko Kitamura,Takachika Hiroi,Hiroyuki Miyoshi,Atsushi Miyawaki,Shoichiro Miyatake,Osamu Kaminuma,Fujiko Kitamura,Noriko Kitamura,Takachika Hiroi,Hiroyuki Miyoshi,Atsushi Miyawaki,Shoichiro Miyatake,

The NFAT family transcription factors play crucial roles in immunological and other biological events; however, the functional differences among NFAT members have not been fully elucidated. This study investigated the relative contribution of NFATc2 and NFATc1 to the transactivation of cytokine genes in T cells. Ectopic expression of NFATc2 but not NFATc1, especially its short isoform, enhanced TNF-alpha synthesis in human T cells at the gene transcription level, whereas both NFATs augmented IL-2 expression. In addition, a reduction of the shortest NFATc1 isoform using RNA interference technology failed to suppress TNF-alpha expression. The promoter/enhancer activity of the NFAT-binding site in the TNF-alpha gene was up-regulated by NFATc2 but not by NFATc1, whereas both NFATs associated similarly with this region. A study of mRNA expression using NFATc2/NFATc1 chimeric molecules revealed that the enhancing activity of NFAT on the TNF-alpha gene was lost by truncation of its C-terminal transactivation domain. In addition, this domain derived from NFATc2 behaved as a dominant negative against the NFAT site in TNF-alpha promoter-dependent transcriptional activity in T cells. We conclude that the C-terminal transactivation domain in NFAT is crucial for TNF-alpha gene expression in human T cells.

Differential Contribution of NFATc2 and NFATc1 to TNF-{alpha} Gene Expression in T Cells. Publishing Authors By Initials

O Kaminuma,F Kitamura,N Kitamura,T Hiroi,H Miyoshi,A Miyawaki,S Miyatake,O Kaminuma,F Kitamura,N Kitamura,T Hiroi,H Miyoshi,A Miyawaki,S Miyatake,

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Differential Contribution of NFATc2 and NFATc1 to TNF-{alpha} Gene Expression in T Cells. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Journal of immunology (Baltimore, Md. : 1950)

VOLUME: 180

Page Numbers: 319-26

Journal Abbreviation: J. Immunol.

ISSN: 0022-1767

DAY: 1

MONTH: Jan

YEAR: 2008

Differential Contribution of NFATc2 and NFATc1 to TNF-{alpha} Gene Expression in T Cells. Information

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LANGUAGE: eng

NlmUniqueID: 2985117

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AFFILIATION: Cytokine Project.

Country: United States

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MEDLINETA: J Immunol

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