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真核起始因子 3:影响人类健康与疾病的重要因素

eIF3: a factor for human health and disease.

机构信息

a Department of Human Genetics , Instituto Nacional de Saúde Doutor Ricardo Jorge , Lisbon , Portugal.

b Gene Expression and Regulation Group, Biosystems & Integrative Sciences Institute (BioISI), Faculdade de Ciências , Universidade de Lisboa , Lisbon , Portugal.

出版信息

RNA Biol. 2018 Jan 2;15(1):26-34. doi: 10.1080/15476286.2017.1391437. Epub 2017 Nov 13.

DOI:10.1080/15476286.2017.1391437
PMID:29099306
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5785978/
Abstract

The eukaryotic initiation factor 3 (eIF3) is one of the most complex translation initiation factors in mammalian cells, consisting of several subunits (eIF3a to eIF3m). It is crucial in translation initiation and termination, and in ribosomal recycling. Accordingly, deregulated eIF3 expression is associated with different pathological conditions, including cancer. In this manuscript, we discuss the interactome and function of each subunit of the human eIF3 complex. Furthermore, we review how altered levels of eIF3 subunits correlate with neurodegenerative disorders and cancer onset and development; in addition, we evaluate how such misregulation may also trigger infection cascades. A deep understanding of the molecular mechanisms underlying eIF3 role in human disease is essential to develop new eIF3-targeted therapeutic approaches and thus, overcome such conditions.

摘要

真核起始因子 3(eIF3)是哺乳动物细胞中最复杂的翻译起始因子之一,由几个亚基(eIF3a 至 eIF3m)组成。它在翻译起始和终止以及核糖体循环中至关重要。因此,eIF3 表达失调与包括癌症在内的不同病理状况有关。在本文中,我们讨论了人 eIF3 复合物每个亚基的互作组和功能。此外,我们还回顾了 eIF3 亚基水平的变化如何与神经退行性疾病和癌症的发生和发展相关;此外,我们还评估了这种失调如何也可能引发感染级联。深入了解 eIF3 在人类疾病中的作用的分子机制对于开发新的 eIF3 靶向治疗方法至关重要,从而克服这些情况。

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Cell Death Dis. 2017 Jun 8;8(6):e2868. doi: 10.1038/cddis.2017.263.
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Human eIF3: from 'blobology' to biological insight.人类真核生物翻译起始因子3:从“团块生物学”到生物学洞察。
Philos Trans R Soc Lond B Biol Sci. 2017 Mar 19;372(1716). doi: 10.1098/rstb.2016.0176.
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Interaction of p190A RhoGAP with eIF3A and Other Translation Preinitiation Factors Suggests a Role in Protein Biosynthesis.p190A RhoGAP与eIF3A及其他翻译起始前因子的相互作用表明其在蛋白质生物合成中发挥作用。
J Biol Chem. 2017 Feb 17;292(7):2679-2689. doi: 10.1074/jbc.M116.769216. Epub 2016 Dec 22.
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Nucleic Acids Res. 2016 Dec 15;44(22):10772-10788. doi: 10.1093/nar/gkw972. Epub 2016 Oct 19.
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Highly expressed ribosomal protein L34 indicates poor prognosis in osteosarcoma and its knockdown suppresses osteosarcoma proliferation probably through translational control.核糖体蛋白 L34 高表达预示着骨肉瘤预后不良,其敲低可能通过翻译调控抑制骨肉瘤增殖。
Sci Rep. 2016 Nov 24;6:37690. doi: 10.1038/srep37690.
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eIF3 Regulation of Protein Synthesis, Tumorigenesis, and Therapeutic Response.真核起始因子3(eIF3)对蛋白质合成、肿瘤发生及治疗反应的调控
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DHX29 and eIF3 cooperate in ribosomal scanning on structured mRNAs during translation initiation.在翻译起始过程中,DHX29和真核生物翻译起始因子3(eIF3)在对结构化信使核糖核酸(mRNA)的核糖体扫描中协同作用。
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