Esnault Stephane, Shen Zhong-Jian, Malter James S
Department of Medicine, Allergy, Pulmonary, and Critical Care Medicine Division, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, United States.
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, United States.
Front Med (Lausanne). 2017 Sep 19;4:150. doi: 10.3389/fmed.2017.00150. eCollection 2017.
We have recently reported that, unlike IL-5 and GM-CSF, IL-3 induces increased translation of a subset of mRNAs. In addition, we have demonstrated that Pin1 controls the activity of mRNA binding proteins, leading to enhanced mRNA stability, GM-CSF protein production and prolonged eosinophil (EOS) survival. In this review, discussion will include an overview of cap-dependent protein translation and its regulation by intracellular signaling pathways. We will address the more general process of mRNA post-transcriptional regulation, especially regarding mRNA binding proteins, which are critical effectors of protein translation. Furthermore, we will focus on (1) the roles of IL-3-driven sustained signaling on enhanced protein translation in EOS, (2) the mechanisms regulating mRNA binding proteins activity in EOS, and (3) the potential targeting of IL-3 signaling and the signaling leading to mRNA binding activity changes to identify therapeutic targets to treat EOS-associated diseases.
我们最近报道,与白细胞介素-5(IL-5)和粒细胞-巨噬细胞集落刺激因子(GM-CSF)不同,白细胞介素-3(IL-3)可诱导一部分mRNA的翻译增加。此外,我们已经证明,肽基脯氨酰顺反异构酶1(Pin1)可控制mRNA结合蛋白的活性,从而增强mRNA稳定性、GM-CSF蛋白生成并延长嗜酸性粒细胞(EOS)存活时间。在本综述中,讨论内容将包括帽依赖性蛋白翻译及其受细胞内信号通路调控的概述。我们将探讨mRNA转录后调控这一更为普遍的过程,尤其是关于mRNA结合蛋白,它们是蛋白翻译的关键效应因子。此外,我们将重点关注:(1)IL-3驱动的持续信号传导对EOS中增强蛋白翻译的作用;(2)调控EOS中mRNA结合蛋白活性的机制;(3)IL-3信号传导以及导致mRNA结合活性变化的信号传导的潜在靶向作用,以确定治疗EOS相关疾病的治疗靶点。