The C-terminal region of human NFATc2 binds dun to synergistically activate interleukin-2 transcription

At eukaryotic promoters multi-faceted protein-protein and protein-DNA interactions can result in synergistic transcriptional activation NFAT and AP-1 proteins Induce interleukin-2 (IL-2) transcription in stimulated T cells but the contributions of individual members of these activator families to synergistically activating IL-2 transcription is not known To investigate the combinatorial regulation of IL-2 transcription we tested the ability of different combinations of NFATc2 NFATc1 dun and cFos to synergistically activate transcription from the IL-2 promoter We found that NFATc2 and chin are exclusive in their ability to synergistically activate human IL-2 transcription Protein-protein interaction assays revealed that in the absence of DNA NFATc2 but not NFATc1 bound directly to cJun/cJun dimers but not to cFos/cJun heterodimers A region of NFATc2 C-terminal of the DNA binding domain was necessary and sufficient for interaction with cJun in the absence of DNA and this same region of NFATc2 was required for the synergistic activation of IL-2 transcription in T cells Moreover expression of this C-terminal region of NFATc2 specifically repressed the synergistic activation of IL-2 transcription These studies show that a previously unidentified interaction between human NFATc2 and cJun is necessary for synergistic activation of IL-2 transcription in T cells (C) 2010 Elsevier Ltd All rights reserved