MECHANISMS OF TRANSACTIVATION BY NUCLEAR FACTOR OF ACTIVATED T-CELLS .1.

Nuclear factor of activated T cells-family proteins (NFAT1/NFATp, NFAT c, NFAT3, and NFAT4/NFATx/NFATc3) play a key role in the transcription of cytokine genes and other genes during the immune response. We have defined the mechanisms of transactivation by NFAT1. NFAT1 possesses t wo transactivation domains whose sequences are riot conserved in the o ther NFAT-family proteins, and a conserved DNA-binding domain that med iates the recruitment of cooperating nuclear transcription factors eve n when it is expressed in the absence of other regions of the protein. The activity of the NH2-terminal transactivation domain is modulated by an adjacent regulatory region that contains several conserved seque nce motifs represented only in the NFAT family. Our results emphasize the multiple levels at which NFAT-dependent transactivation is regulat ed, and predict significant differences in the architecture of coopera tive transcription complexes containing different NFAT-family proteins .