Cytokine gene regulation by NFAT
Point mutations in the transcription factor NFAT define sets of cytokine genes whose regulation is dependent on or independent of cooperation between NFAT and Fos/Jun
Cooperation between nuclear factor of activated T cells (NFAT) and the Fos/Jun transcription factors is central to integrating converging signals upon lymphocyte activation. In the 1 September EMBO Journal Macian et al, engineered mutants of NFAT1 that no longer interact with Fos/Jun dimers, but still bind DNA and activate transcription. These proved to be powerful tools for defining the need for NFAT–Fos–Jun cooperation in regulating cytokine gene expression. The target genes for NFAT can be divided into those that absolutely require cooperation for activation (for example, the genes for interleukin (IL)-2, GM-CSF, IL-3, IL-4 and FasL), and those that are induced by NFAT alone (for example, TNFalpha and IL-13). Cooperation is also functionally important for activation-induced cell death of lymphocytes. These results have therapeutic implications for the development of more specific immunosuppressive drugs.