NFAT and NF-κB factors—the distant relatives

Abstract NFAT and NF-κB proteins are members of a superfamily of transcription factors whose activity plays a crucial role in the activation, proliferation and apoptosis of lymphocytes. Both types of factors share a number of properties, including similar DNA binding domains and rapid nuclear translocation upon antigenic stimulation. While NF-κBs control both innate and adaptive immune responses, NFATs control the adaptive immune system which emerged—in parallel with the appearance of the NFAT family—in jawed fish. However, NFATs and NF-κBs differ remarkably in their function. Whereas NFATs support activation-induced cell death (AICD) of T and B cells, NF-κB proteins frequently exert a strong anti-apoptotic effect on lymphocytes and other cells. While the anti-apoptotic activity of NF-κBs contributes to their oncogenic capacity, the pro-apoptotic activity favors NFATs as tumor suppressors in lymphoid cells.