RA-inducible gene-I induction augments STAT1 activation to inhibit leukemia cell proliferation
RA-inducible gene-I induction augments STAT1 activation to inhibit leukemia cell proliferation
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RA诱导基因-I诱导增强STAT1激活以抑制白血病细胞增殖
DOI：
10.1073/pnas.1019059108
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发表时间：
2011-02-01
影响因子：
11.1
通讯作者：
Zhu, Jiang
中科院分区：
文献类型：
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作者：
Jiang, Lin-Jia;Zhang, Nan-Nan;Zhu, Jiang
RA诱导基因I（RIG-I/DDX 58）已显示在识别细胞质病毒RNA时激活IFN-β启动子刺激因子1（IPS-1）。目前还不清楚RIG-I如何在急性髓性白血病（AML）细胞中的IFN和/或RA信号传导过程中起作用，然而，在那里观察到明显的RIG-I诱导。在这里，我们表明，RIG-I诱导功能有助于IFN-α加RA触发的AML细胞的生长抑制。有趣的是，虽然RIG-I诱导本身是在STAT 1（一种主要的IFN细胞内信号介导物）的调节下，但在其不刺激IPS-1的情况下，它反过来增强STAT 1活化以诱导IFN刺激性基因表达并抑制白血病细胞增殖。因此，我们的研究结果揭示了以前未描述的RIG-I活性通过STAT 1调节白血病细胞的细胞增殖，这是独立于其经典的传感病毒入侵触发I型IFN转录的作用。
RA-inducible gene I (RIG-I/DDX58) has been shown to activate IFN-beta promoter stimulator 1 (IPS-1) on recognizing cytoplasmic viral RNAs. It is unclear how RIG-I functions within the IFN and/or RA signaling process in acute myeloid leukemia (AML) cells, however, where obvious RIG-I induction is observed. Here, we show that the RIG-I induction functionally contributes to IFN-alpha plus RA-triggered growth inhibition of AML cells. Interestingly, although RIG-I induction itself is under the regulation of STAT1, a major IFN intracellular signal mediator, under circumstances in which it does not stimulate IPS-1, it conversely augments STAT1 activation to induce IFN-stimulatory gene expression and inhibit leukemia cell proliferation. Thus, our results unveil a previously undescribed RIG-I activity in regulating the cellular proliferation of leukemia cells via STAT1, which is independent of its classic role of sensing viral invasion to trigger type I IFN transcription.