Luo C, Shaw K T, Raghavan A, Aramburu J, Garcia-Cozar F, Perrino B A, Hogan P G, Rao A
Division of Cellular and Molecular Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):8907-12. doi: 10.1073/pnas.93.17.8907.
The nuclear import of the nuclear factor of activated T cells (NFAT)-family transcription factors is initiated by the protein phosphatase calcineurin. Here we identify a regulatory region of NFAT1, N terminal to the DNA-binding domain, that controls nuclear import of NFAT1. The regulatory region of NFAT1 binds directly to calcineurin, is a substrate for calcineurin in vitro, and shows regulated subcellular localization identical to that of full-length NFAT1. The corresponding region of NFATc likewise binds calcineurin, suggesting that the efficient activation of NFAT1 and NFATc by calcineurin reflects a specific targeting of the phosphatase to these proteins. The presence in other NFAT-family transcription factors of several sequence motifs from the regulatory region of NFAT1, including its probable nuclear localization sequence, indicates that a conserved protein domain may control nuclear import of all NFAT proteins.
活化T细胞核因子（NFAT）家族转录因子的核输入由蛋白磷酸酶钙调神经磷酸酶启动。在此，我们鉴定出NFAT1位于DNA结合结构域N端的一个调控区域，该区域控制NFAT1的核输入。NFAT1的调控区域直接与钙调神经磷酸酶结合，在体外是钙调神经磷酸酶的底物，并且显示出与全长NFAT1相同的亚细胞定位调控。NFATc的相应区域同样与钙调神经磷酸酶结合，这表明钙调神经磷酸酶对NFAT1和NFATc的有效激活反映了该磷酸酶对这些蛋白的特异性靶向作用。在其他NFAT家族转录因子中存在来自NFAT1调控区域的几个序列基序，包括其可能的核定位序列，这表明一个保守的蛋白结构域可能控制所有NFAT蛋白的核输入。
