活化T细胞核因子-1的反式激活机制
Mechanisms of transactivation by nuclear factor of activated T cells-1.
作者信息
Luo C, Burgeon E, Rao A
机构信息
Division of Cellular and Molecular Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
出版信息
J Exp Med. 1996 Jul 1;184(1):141-7. doi: 10.1084/jem.184.1.141.
Abstract
Nuclear factor of activated T cells-family proteins (NFAT1/NFATp, NFATc, NFAT3, and NFAT4/NFATx/NFATc3) play a key role in the transcription of cytokine genes and other genes during the immune response. We have defined the mechanisms of transactivation by NFAT1. NFAT1 possesses two transactivation domains whose sequences are not conserved in the other NFAT-family proteins, and a conserved DNA-binding domain that mediates the recruitment of cooperating nuclear transcription factors even when it is expressed in the absence of other regions of the protein. The activity of the NH2-terminal transactivation domain is modulated by an adjacent regulatory region that contains several conserved sequence motifs represented only in the NFAT family. Our results emphasize the multiple levels at which NFAT-dependent transactivation is regulated, and predict significant differences in the architecture of cooperative transcription complexes containing different NFAT-family proteins.
摘要
活化T细胞核因子家族蛋白（NFAT1/NFATp、NFATc、NFAT3以及NFAT4/NFATx/NFATc3）在免疫反应过程中，对细胞因子基因及其他基因的转录起着关键作用。我们已经明确了NFAT1反式激活的机制。NFAT1拥有两个反式激活结构域，其序列在其他NFAT家族蛋白中并不保守，还有一个保守的DNA结合结构域，即便在该蛋白其他区域缺失的情况下表达，它也能介导协同核转录因子的募集。NH2末端反式激活结构域的活性受相邻调控区域的调节，该调控区域包含几个仅在NFAT家族中存在的保守序列基序。我们的研究结果强调了NFAT依赖性反式激活受调控的多个层面，并预测了含有不同NFAT家族蛋白的协同转录复合物在结构上存在显著差异。
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