Upregulation of AP-1 activity by C-rel

C-rel is critical for IL-2 induction in T lymphocytes and is upregulated following T cell receptor stimulation. We examined the effect of c-rel on the activity of several transcription factors which bind to the IL-2 promoter. While c-rel overexpression did not affect the activity of Oct, ARRE-1 or NFAT reporter constructs, it increased transcription from an AP-1 reporter construct by 20-fold, an extent as great as T cell receptor stimulation. In contrast, p65 overexpression had only a 3-fold effect on AP-1 activity. Interestingly, c-rel activated an NF-KB reporter to a much lesser extent than an AP-1 reporter. Both the DNA binding and transactivation domains of c-rel were required for its effect on AP-1. This effect is most likely indirect, as direct binding of c-rel to an AP-1 oligo could not be demonstrated. These observations may help explain how c-rel regulates IL-2 expression.