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Kaminuma, O. et al.

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

Differential contribution of NFATc2 and NFATc1 to TNF-alpha gene expression in T cells.

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.[1]

References

Differential contribution of NFATc2 and NFATc1 to TNF-alpha gene expression in T cells. Kaminuma, O., Kitamura, F., Kitamura, N., Hiroi, T., Miyoshi, H., Miyawaki, A., Miyatake, S. J. Immunol. (2008) [Pubmed]

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