IFN-γ-stimulated transcriptional activation by IFN-γ-activated transcriptional element-binding factor 1 occurs via an inducible interaction with CAAAT/enhancer-binding protein-β
IFN-γ-stimulated transcriptional activation by IFN-γ-activated transcriptional element-binding factor 1 occurs via an inducible interaction with CAAAT/enhancer-binding protein-β
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DOI：
10.4049/jimmunol.174.10.6203
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发表时间：
2005-05-15
影响因子：
4.4
通讯作者：
Kalvakolanu, DV
中科院分区：
文献类型：
--
作者：
Meng, QJ;Raha, A;Kalvakolanu, DV
IFN-γ激活的转录元件（GATE）结合因子1（GBF 1）被鉴定为通过GATE（一种新的IFN诱导元件）诱导基因表达的反式激活因子。虽然它可以诱导基因表达，但它本身是一种非常弱的DNA结合蛋白。GATE还结合另一种转录因子C/EBP-β。因此，我们探讨了GBF 1是否与C/EBP-β物理相互作用以诱导IFN-γ调节的转录。在对IFN-γ的应答中，C/EBP-β在关键的ERK 1/2磷酸化基序处经历磷酸化。该基序的突变失活和/或对ERK 1/2活化的干扰阻止了IFN-γ诱导的GBF 1和C/EBP-β之间的相互作用。来自GBF 1蛋白的37-aa长的肽可以以IFN-诱导的方式与C/EBP-P结合。这些结果确定了两个反式激活因子通过一个单一的反应元件发挥其作用的一个汇聚点。总之，我们的研究确定了一种新的调控机制，控制干扰素诱导的转录。
IFN-gamma-activated transcriptional element (GATE)-binding factor 1 (GBF1) was identified as a transactivator that induces gene expression through GATE, a novel IFN-inducible element. Although it can induce gene expression, it is an extremely weak DNA-binding protein on its own. GATE also binds another transcription factor, C/EBP-beta. Therefore, we explored whether GBF1 physically interacts with C/EBP-beta to induce IFN-gamma-regulated transcription. In response to IFN-gamma, C/EBP-beta undergoes phosphorylation at a critical ERK1/2 phosphorylation motif. Mutational inactivation of this motif and/or interference with the ERK1/2 activation prevented the IFN-gamma-induced interactions between GBF1 and C/EBP-beta. A 37-aa long peptide derived from the GBF1 protein can associate with C/EBP-P in an IFN-inducible manner. These results identify a converging point for two transactivators that exert their effects through a single response element. Together, our studies identify a novel regulatory mechanism that controls IFN-induced transcription.