NF-AT COMPONENTS DEFINE A FAMILY OF TRANSCRIPTION FACTORS TARGETED IN T-CELL ACTIVATION

THE NF-AT transcription complex(1) is required far the expression of a group of proteins that collectively coordinate the immune response(2-4). Here we purify two proteins encoded by separate genes that represent the pre-existing (p) and cytosolic (c) components of NF-AT. Expression of the full-length complementary DNA encoding NF-AT(c) activates the interleukin (IL-2) promoter in non-T lymphocytes, whereas a dominant negative of NF-AT(c), specifically blocks activation of the IL-2 promoter in T lymphocytes, indicating that NF-AT(c) is required for IL-2 gene expression. NF-AT(c) RNA expression is largely restricted to lymphoid tissues and is induced upon T-cell activation. The other protein, NF-AT(p), is highly homologous to NF-AT(c) over a limited domain which shows similarity to the Dorsal/Rel family(5), but has a wider tissue distribution. Agents that increase intracellular Ca2+ or activate protein kinase C independently modify NF-AT(c), indicating that distinct signalling pathways converge on NF-AT(c) to regulate its function.