Insights into the role of collided ribosomes during the activation of the integrated stress response.

IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Ankanahalli N Nanjaraj Urs, Lucas Kim, Hani S Zaher
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引用次数: 0

Abstract

Mechanisms that regulate and reprogram gene expression are particularly important under stress conditions. The integrated stress response (ISR) signaling pathway is one such pro-survival and adaptive mechanism conserved in eukaryotes. The ISR is characterized by the activation of protein kinases that phosphorylate the eukaryotic initiation factor 2α (eIF2α) in response to several stress conditions, including nutrient deprivation, viral infection, and protein misfolding. Phosphorylation of eIF2α results in global inhibition of translation, while promoting the translation of a few pro-survival genes. Here, we focus on the mechanism of activation of the eIF2α kinase general control nonderepressible 2 (Gcn2). The protein was initially discovered in yeast more than four decades ago, and it was proposed to respond to amino acid starvation through the accumulation of deacylated tRNAs. However, more recent studies have changed our understanding of its activation and suggest a direct role for ribosome stalling and collisions in the process. In this review, we discuss the classical model for the tRNA-mediated activation of GCN2 and the recent shift in this model to accommodate the observations that wide-ranging translational stresses trigger its activation.

在综合应激反应的激活过程中碰撞核糖体的作用。
调控和重编程基因表达的机制在应激条件下尤为重要。综合应激反应(integrated stress response, ISR)信号通路是真核生物中保守的一种促生存和适应性机制。ISR的特征是在多种应激条件下(包括营养剥夺、病毒感染和蛋白质错误折叠)激活真核起始因子2α (eIF2α)磷酸化的蛋白激酶。eIF2α的磷酸化导致翻译的全局抑制,同时促进少数促生存基因的翻译。在这里,我们重点研究了eIF2α激酶一般控制非抑制2 (Gcn2)的激活机制。四十多年前,这种蛋白质最初在酵母中被发现,并被提出通过脱酰基trna的积累来应对氨基酸饥饿。然而,最近的研究改变了我们对其激活的理解,并提出了核糖体在这一过程中的失速和碰撞的直接作用。在这篇综述中,我们讨论了trna介导的GCN2激活的经典模型,以及该模型最近的转变,以适应广泛的翻译应激触发其激活的观察结果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Biochemical Society transactions
Biochemical Society transactions 生物-生化与分子生物学
CiteScore
7.80
自引率
0.00%
发文量
351
审稿时长
3-6 weeks
期刊介绍: Biochemical Society Transactions is the reviews journal of the Biochemical Society. Publishing concise reviews written by experts in the field, providing a timely snapshot of the latest developments across all areas of the molecular and cellular biosciences. Elevating our authors’ ideas and expertise, each review includes a perspectives section where authors offer comment on the latest advances, a glimpse of future challenges and highlighting the importance of associated research areas in far broader contexts.
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