NF-AT components define a family of transcription factors targeted in T-cell activation

Abstract

THE NF-AT transcription complex¹ is required for 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 enco-ding 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 homo-logous to NF-AT_c over a limited domain which shows similarity to the Dorsal/Rel family⁵, 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.