NUCLEAR FACTOR OF ACTIVATED T-CELLS CONTAINS FOS AND JUN
NUCLEAR FACTOR OF ACTIVATED T-CELLS CONTAINS FOS AND JUN
复制标题
DOI：
10.1038/356801a0
复制
发表时间：
1992-04-30
期刊：
影响因子：
64.8
通讯作者：
RAO, A
中科院分区：
文献类型：
--
作者：
JAIN, J;MCCAFFREY, PG;RAO, A
核因子NF-AT（参考文献1）通过T细胞受体/CD 3复合物在刺激的T细胞中被诱导，并且是白细胞介素-2（IL-2）基因诱导所必需的。尽管NF-AT尚未被克隆或纯化，但有证据表明它是环孢菌素A（CsA）和FK 506免疫抑制的主要靶点（参考文献2-7）。NF-AT诱导可能需要两个激活依赖性事件：预先存在的组分的CsA敏感性易位和核组分的CsA抗性合成8。在这里，我们报告说，新合成的核组件的NF-AT是转录因子AP-1。我们发现，诱导核形式的NF-AT含有Fos和Jun蛋白。此外，我们确定了一个预先存在的NF-AT结合因子，存在于低渗提取物的未刺激的T细胞。结合，重建和共转染实验的基础上，我们提出，激活的NF-AT发生在至少两个阶段：CsA敏感的阶段，涉及修改和/或易位的预先存在的NF-AT复合物，和CsA不敏感的阶段，涉及添加新合成的Fos或Fos/Jun蛋白的预先存在的复合物。
THE nuclear factor NF-AT (ref. 1) is induced in T cells stimulated through the T-cell receptor/CD3 complex, and is required for interleukin-2 (IL-2) gene induction. Although NF-AT has not been cloned or purified, there is evidence that it is a major target for immunosuppression by cyclosporin A (CsA) and FK506 (refs 2-7). NF-AT induction may require two activation-dependent events: the CsA-sensitive translocation of a pre-existing component and the CsA-resistant synthesis of a nuclear component 8. Here we report that the newly synthesized nuclear component of NF-AT is the transcription factor AP-1. We show that the inducible nuclear form of NF-AT contains Fos and Jun proteins. Furthermore, we identify a pre-existing NF-AT-binding factor that is present in hypotonic extracts of unstimulated T cells. On the basis of binding, reconstitution and cotransfection experiments, we propose that activation of NF-AT occurs in at least two stages: a CsA-sensitive stage involving modification and/or translocation of the pre-existing NF-AT complex, and a CsA-insensitive stage involving the addition of newly synthesized Fos or Fos/Jun proteins to the pre-existing complex.