Masuda E S, Naito Y, Tokumitsu H, Campbell D, Saito F, Hannum C, Arai K, Arai N
Department of Cell Biology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, California 94304, USA.
Mol Cell Biol. 1995 May;15(5):2697-706. doi: 10.1128/MCB.15.5.2697.
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.
活化T细胞核因子(NFAT)通过位于细胞因子基因启动子中的顺式作用元件调节T细胞中的细胞因子基因表达。在此,我们报告一种与NFATp和NFATc相关的转录因子的cDNA克隆、染色体定位及初步特性。这种新分子命名为NFATx,在其中间区域有一个与NFATc和NFATp中的Rel同源结构域非常相似的区域。NFATx的氨基末端区域也与NFATc和NFATp中的相应序列有显著相似性,并包含三个功能未知的明显的17个氨基酸残基基序拷贝。我们提供的证据表明,NFATx与AP1(c-Fos/c-Jun)多肽结合时可重建与白细胞介素2启动子中NFAT结合位点的结合,并且在用佛波酯和钙离子载体刺激时,NFATx能够在COS-7细胞中激活白细胞介素2启动子的转录。NFATx mRNA在胸腺中优先且显著表达,在外周血白细胞中表达水平较低。NFATx的表达模式及其功能活性强烈表明,NFATx在T细胞和未成熟胸腺细胞的基因表达调控中发挥作用。