Robert H. Lurie Comprehensive Cancer Center and Division of Hematology-Oncology, Northwestern University Medical School, and Jesse Brown VA Medical Center, Chicago, IL, USA.
Cytokine. 2010 Oct-Nov;52(1-2):123-7. doi: 10.1016/j.cyto.2010.03.019. Epub 2010 Apr 20.
Over the last two decades, a lot of research work has been focused on the interferon (IFN)-regulated JAK-STAT pathway and understanding the mechanisms governing the transcription of interferon stimulated genes (ISGs). Evidence suggests that the JAK-STAT pathway alone does not account in its entirety for mediating cellular responses to IFNs. There is emerging evidence that non-Stat pathways play important roles in mediating signals for the generation of IFN-responses. Various studies have underscored the importance of mitogen activated protein kinases (MAPKs), especially p38 and ERK1/2, as well as the PI 3'K/AKT pathway in transmitting signals that are of critical importance for the biological effects of IFNs. Besides regulating the transcription of ISGs in some cases, engagement of these signaling pathways by the IFN-receptor (IFNR) associated complexes also plays an important role in mediating the translation of ISGs. The mechanisms regulating mRNA translation of ISGs is an area of ongoing active research and a lot more efforts will be required to complete our understanding of the various cellular elements involved in this process. In this review we highlight the mechanisms regulating translation of ISGs. We focus on the proteins regulated by the PI 3'K/AKT pathway, their role in mediating mRNA translation of ISGs and the functional consequences of this regulation. In addition, MAPKs are known to regulate the phosphorylation of various eukaryotic initiation factors and we summarize the roles of eIF4B and eIF4E phosphorylations on the translation of ISGs. The emerging roles of microRNAs in mRNA translation of ISGs are also discussed.
在过去的二十年中，大量的研究工作集中在干扰素（IFN）调节的 JAK-STAT 途径上，并致力于理解调控干扰素刺激基因（ISGs）转录的机制。有证据表明，JAK-STAT 途径本身并不能完全解释细胞对干扰素的反应。有新的证据表明，非 Stat 途径在介导产生 IFN 反应的信号方面发挥着重要作用。各种研究强调了丝裂原活化蛋白激酶（MAPKs），特别是 p38 和 ERK1/2，以及 PI 3'K/AKT 途径在传递对 IFN 生物学效应至关重要的信号方面的重要性。除了在某些情况下调节 ISGs 的转录外，IFN 受体（IFNR）相关复合物与这些信号通路的结合也在介导 ISGs 的翻译中起着重要作用。ISGs 的 mRNA 翻译的调控机制是一个正在进行的积极研究领域，需要更多的努力来完成我们对涉及该过程的各种细胞成分的理解。在这篇综述中，我们强调了调节 ISGs 翻译的机制。我们专注于受 PI 3'K/AKT 途径调节的蛋白质，它们在介导 ISGs 的 mRNA 翻译中的作用，以及这种调节的功能后果。此外，MAPKs 已知调节各种真核起始因子的磷酸化，我们总结了 eIF4B 和 eIF4E 磷酸化在 ISGs 翻译中的作用。还讨论了 microRNAs 在 ISGs 的 mRNA 翻译中的新兴作用。
