NFATx, a Novel Member of the Nuclear Factor of Activated T Cells Family That Is Expressed Predominantly in the Thymus

Abstract

The nuclear factor of activated T cells (NFAT) regulates cytokine gene expression in T cells through cis-acting elements located in the promoters of cytokine genes. Here, we report the cDNA cloning, chromosomal localization, and initial characterization of a transcription factor related to NFATp and NFATc. The novel molecule, designated NFATx, exhibits in its middle a region very similar to the Rel homology domain in NFATc and NFATp. The amino-terminal region of NFATx also shows significant similarities to corresponding sequences in NFATc and NFATp and contains three copies of a conspicuous 17-residue motif of unknown function. We provide evidence showing that NFATx can reconstitute binding to the NFAT-binding site from the interleukin 2 promoter when combined with AP1 (c-Fos/c-Jun) polypeptides and that NFATx is capable of activating transcription of the interleukin 2 promoter in COS-7 cells when stimulated with phorbol ester and calcium ionophore. NFATx mRNA is preferentially and remarkably found in the thymus and at lower levels in peripheral blood leukocytes. The expression pattern of NFATx, together with its functional activity, strongly suggests that NFATx plays a role in the regulation of gene expression in T cells and immature thymocytes.

Effect of Moderate Acute Exercise on Expression of mRNA Involved in the Calcineurin Signaling Pathway in Human Skeletal Muscle

“…Although this approach does not allow absolute quantification of the amount of mRNA, it is useful for comparing relative expression levels between mRNA species of interest. In the calcineurin A and NFAT families, calcineurin Abe, NFAT4 (13), and NFAT5 (14) were the predominant isoforms expressed in human skeletal muscle. Interestingly, the mRNA expression of NFAT4 and NFAT5 was higher than that of NFAT2, although NFAT2 has been regarded as an important isoform in skeletal muscle development and differentiation (3).…”

Dynamic equilibrium between calcineurin and kinase activities regulates the phosphorylation state and localization of the nuclear factor of activated T-cells

“…Activation of these genes is mediated in part by nuclear factor of activated T-cells (NFAT), a DNA-binding protein that binds to specific sites on the regulatory regions of these genes (reviewed in [1,2]). Molecular cloning studies have demonstrated that at least four different NFAT genes exist, including NFAT p , NFAT c , NFAT3 and NFAT x , all of which contain a Rel homology region that is important for DNA binding [3][4][5][6]. In addition, a serine\proline repeat region of unknown function is present in each of the family members, as well as a putative nuclear localization sequence.…”

“…In addition, a serine\proline repeat region of unknown function is present in each of the family members, as well as a putative nuclear localization sequence. The exact biological function of each of the NFAT proteins is not known, although differences in cell and tissue expression, as well as DNA-binding activity, have been observed [3,7,8].…”

The Bcl-2 gene is differentially regulated by IL-2 and IL-4: role of the transcription factor NF-AT

“…As for several other transcription factors, NF-AT activity appears to be regulated by subcellular localization and phosphorylation events (Clipstone and Crabtree, 1992) and by interactions between calcineurin and Bcl-2 (Shibasaki et al, 1997). NF-AT is composed of the transcription factor AP-1 and a cytoplasmic subunit, the latter encoded by a family of genes including NFATp, NF-ATc, NF-AT3 and NF-AT4/x Masuda et al, 1995;Northrop et al, 1994). The family members share approximately 70% sequence identity within a region related to the Rel homology domain of the NF-kB transcription factors Northrop et al, 1994).…”