NFAT5, a constitutively nuclear NFAT protein that does not cooperate with Fos and Jun

NFAT transcription factors are related to NF-kappa B/Rel proteins and form cooperative complexes with Fos and Jun on DNA. We have identified an NFAT-r elated protein, NFAT5, which differs from the conventional NFAT proteins NF AT1-4 in its structure, DNA binding, and regulation. NFAT5 contains a NFAT- like Rel homology domain, conserves the DNA contact residues of NFAT1-4, an d binds DNA sequences similar to those found in the regulatory regions of w ell-eharacterized NFAT-dependent genes. However, it lacks the majority of F os/Jun contact residues and does not bind cooperatively with Fos and Jun to DNA. Unlike NFAT1-4 whose nuclear import is tightly regulated by calcineur in-mediated dephosphorylation, NFAT5 is a constitutively nuclear phosphopro tein regardless of calcineurin activation. These features suggest that unli ke the conventional NFAT proteins, NFAT1-4, which activate gene transcripti on by integrating inputs from calcium/calcineurin and protein kinase C/mito gen-activated protein kinase signaling pathways, NFAT5 participates in as-y et-unidentified signaling pathways in diverse immune and nonimmune cells.