2 DISTINCT ALPHA-INTERFERON-DEPENDENT SIGNAL TRANSDUCTION PATHWAYS MAY CONTRIBUTE TO ACTIVATION OF TRANSCRIPTION OF THE GUANYLATE-BINDING PROTEIN GENE
2 DISTINCT ALPHA-INTERFERON-DEPENDENT SIGNAL TRANSDUCTION PATHWAYS MAY CONTRIBUTE TO ACTIVATION OF TRANSCRIPTION OF THE GUANYLATE-BINDING PROTEIN GENE
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DOI：
10.1128/mcb.11.10.5147
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发表时间：
1991-10-01
影响因子：
5.3
通讯作者：
DARNELL, JE
中科院分区：
文献类型：
--
作者：
DECKER, T;LEW, DJ;DARNELL, JE
编码胞质鸟苷结合蛋白(GBP)基因的启动子包含两个重叠的元件：干扰素刺激反应元件(ISRE)和干扰素-γ激活位点(GAS)，前者介导α-干扰素依赖的转录，后者是干扰素-γ介导的刺激所必需的。ISRE结合一种名为ISGF-3的因子，该因子可被干扰素-α激活，但不能被干扰素-γ激活。这种气体结合了一种由干扰素-伽马激活的蛋白质，我们称之为GAF(干扰素-伽马激活因子；T.Decker，D.J.Lew，J.Mirkovitch，and J.E.Darnell，Jr.，EMBO J.；D.J.Lew，T.Decker，I.Strehlow和J.E.Darnell，Jr.，Mol.)。牢房。比奥尔。11：182-191,1991)。我们现在发现，GAS在体内也是一个干扰素-α反应元件，并且干扰素-α(除了激活ISGF-3外)还能迅速激活气体结合因子--干扰素-α激活因子(AAF)。AAF具有与前面描述的GAF非常相似的特性。通过使用蛋白质合成抑制剂和蛋白激酶抑制剂，可以区分AAF、GAF和ISGF-3的激活条件。因此，干扰素-α和干扰素-γ不仅通过连接到不同信号分子的不同受体刺激GBP的转录，而且干扰素-α受体的占据显然通过不同的细胞内途径导致两种不同的DNA结合蛋白的快速激活。
The promoter of the gene encoding a cytoplasmic guanylate-binding protein (GBP) contains two overlapping elements: the interferon stimulation response element (ISRE), which mediates alpha interferon (IFN-alpha)-dependent transcription, and the IFN-gamma activation site (GAS), which is required for IFN-gamma-mediated stimulation. The ISRE binds a factor called ISGF-3 that is activated by IFN-alpha but not by IFN-gamma. The GAS binds a protein that is activated by IFN-gamma, which we have termed GAF (IFN-gamma activation factor; T. Decker, D. J. Lew, J. Mirkovitch, and J. E. Darnell, Jr., EMBO J., in press; D. J. Lew, T. Decker, I. Strehlow, and J.E. Darnell, Jr., Mol. Cell. Biol. 11:182-191, 1991). We now find that the GAS is also an IFN-alpha-responsive element in vivo and that IFN-alpha (in addition to activating ISGF-3) rapidly activates a GAS-binding factor, the IFN-alpha activation factor (AAF). The AAF has characteristics very similar to those of the previously described GAF. Through the use of inhibitors of protein synthesis and inhibitors of protein kinases, the activation conditions of AAF, GAF, and ISGF-3 could be distinguished. Therefore, not only do IFN-alpha and IFN-gamma stimulate transcription of GBP through different receptors linked to different signaling molecules, but occupation of the IFN-alpha receptor apparently leads to the rapid activation of two different DNA-binding proteins through the use of different intracellular pathways.