A SIMILAR DNA-BINDING MOTIF IN NFAT FAMILY PROTEINS AND THE REL HOMOLOGY REGION

The cyclosporin-sensitive factor NFATp cooperates with Fos and Jun fam ily proteins to regulate transcription of the interleukin 2 gene in ac tivated T cells. We have defined a 187-amino acid fragment of NFATp, l ocated centrally within the protein sequence, as the minimal region re quired for DNA binding and for complex formation with Fos and Jun. The sequence of this region of NFATp shows a low degree of similarity to the Rel homology region. One specific short sequence in NFATp (RAHYETE G), located near the NH, terminus of the DNA-binding domain, resembles a highly conserved sequence (RFRYxCEG) that is located near the NH, t erminus of the Rel homology region and that has been implicated in DNA binding by Rel family proteins. Mutational analysis demonstrates that the residues in this sequence that are identical in NFATp, and Rel fa mily proteins contribute to DNA binding by NFATp. Further, mutation of the threonine residue in this sequence to cysteine, as in Rel protein s, confers on NFATp a sensitivity to sulfhydryl modification similar t o that of Rel family proteins. The results suggest that NFATp and Rel family proteins bind to DNA using similar structural motifs.