NFATC3, A LYMPHOID-SPECIFIC NFATC FAMILY MEMBER THAT IS CALCIUM-REGULATED AND EXHIBITS DISTINCT DNA FINDING SPECIFICITY
NFATC3, A LYMPHOID-SPECIFIC NFATC FAMILY MEMBER THAT IS CALCIUM-REGULATED AND EXHIBITS DISTINCT DNA FINDING SPECIFICITY
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DOI：
10.1074/jbc.270.34.19898
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发表时间：
1995-08-25
影响因子：
4.8
通讯作者：
CRABTREE, GR
中科院分区：
文献类型：
--
作者：
HO, SN;THOMAS, DJ;CRABTREE, GR
由T细胞抗原受体(TCR)转导的信号调节胸腺的发育转变，也介导成熟的外周T细胞的免疫激活，在这两种情况下，TCR的刺激导致NFAT转录复合体的组装，这是胞浆亚基NFATc和Ras/蛋白激酶C依赖的核亚基NFATn诱导的结果。为了进一步了解抗原受体信号在T细胞发育过程中的不同作用，我们鉴定了一个新的NFATc家族成员NFATc3，它在胸腺中表达水平最高。NFATc3是小鼠8号染色体上的一个基因的产物，该基因与其他NFATc基因没有关联。NFATc3和其他NFATc家族成员一样，包含一个保守的REL相似结构域，也定义了一个在NFATc家族成员中保守的区域，即SP重复区域，其特征是重复基序SPxxSPxxSPrx-SXX(D/E)(D/E)SWL。NFATc3在过度表达时激活NFAT位点依赖的转录，但表现出与其他NFATc蛋白不同的DNA位点特异性模式，此外，胸腺NFATc3经历了模拟T细胞受体信号转导的药物的修饰，包括当细胞内钙升高时表观分子质量下降，这被免疫抑制剂FK506抑制，由于NFATc3在胸腺中的优先表达，NFATc家族成员可能在T细胞发育过程中调节不同的基因亚群。
Signals transduced by the T cell antigen receptor (TCR) regulate developmental transitions in the thymus and also mediate the immunologic activation of mature, peripheral T cells, In both cases TCR stimulation leads to the assembly of the NFAT transcription complex as a result of the calcium-dependent nuclear translocation of cytosolic subunits, NFATc, and the Ras/protein kinase C-dependent induction of a nuclear subunit, NFATn, To further understand the diverse roles of antigen receptor signaling throughout T cell development, we have identified a new NFATc family member, NFATc3, that is expressed at highest levels in the thymus, NFATc3 is the product of a gene on murine chromosome 8 that is not Linked to the other NFATc genes. NFATc3, like other NFATc family members, contains a conserved rel similarity domain, and also defines a region conserved among NFATc family members, the SP repeat region, characterized by the repeated motif SPxxSPxxSPrx-sxx(D/E)(D/E)swl. NFATc3 activates NFAT site-dependent transcription when overexpressed, yet exhibits a pattern of DNA site specificity distinct hom other NFATc proteins, Additionally, thymic NFATc3 undergoes modifications in response to agents that mimic T cell receptor signaling, including a decrease in apparent molecular mass upon elevation of intracellular calcium that is inhibited by the immunosuppressant FK506, Given the preferential expression of NFATc3 in the thymus, NFATc family members may regulate distinct subsets of genes during T cell development.