Wong A H, Tam N W, Yang Y L, Cuddihy A R, Li S, Kirchhoff S, Hauser H, Decker T, Koromilas A E
Department of Oncology, McGill University, Montreal, Quebec, Canada.
EMBO J. 1997 Mar 17;16(6):1291-304. doi: 10.1093/emboj/16.6.1291.
The interferon-inducible double-stranded RNA protein kinase PKR controls protein synthesis through the phosphorylation of eukaryotic translation initiation factor (eIF)-2. In addition to its demonstrated role in translational control, several reports have suggested a transcriptional role for PKR. Here we report that PKR is involved in IFN- and dsRNA-signaling pathways by modulating the function of the signal transducer and activator of transcription STAT1. We also show that PKR associates with STAT1 in mouse and human cells. The association is not a kinase-substrate interaction since STAT1 phosphorylation is not modified by PKR in vitro or in vivo. In addition, the formation of the PKR-STAT1 complex is not dependent upon the enzymatic activity of PKR but does require the dsRNA-binding domain of PKR. Moreover, there is a concomitant decrease in PKR-STAT1 interaction and increase in STAT1 DNA binding in response to IFNs or dsRNA. These findings suggest that PKR plays an important role in IFN and dsRNA-signaling pathways by modulating the transcriptional function of STAT1.
干扰素诱导的双链RNA蛋白激酶PKR通过真核翻译起始因子（eIF）-2的磷酸化来控制蛋白质合成。除了其在翻译控制中已证实的作用外，一些报道还提示PKR具有转录作用。在此我们报告，PKR通过调节信号转导及转录激活因子STAT1的功能而参与干扰素和双链RNA信号通路。我们还表明，PKR在小鼠和人类细胞中与STAT1相互关联。这种关联并非激酶-底物相互作用，因为在体外或体内PKR均未改变STAT1的磷酸化。此外，PKR-STAT1复合物的形成不依赖于PKR的酶活性，但确实需要PKR的双链RNA结合结构域。而且，响应干扰素或双链RNA时，PKR-STAT1相互作用会随之减少，而STAT1与DNA的结合会增加。这些发现提示，PKR通过调节STAT1的转录功能在干扰素和双链RNA信号通路中发挥重要作用。
