Pellegrino Simone, Terrosu Salvatore, Yusupova Gulnara, Yusupov Marat
Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK.
Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR7104, Université de Strasbourg, 67404 Illkirch, France.
Cancers (Basel). 2021 Aug 31;13(17):4392. doi: 10.3390/cancers13174392.
Protein biosynthesis is a vital process for all kingdoms of life. The ribosome is the massive ribonucleoprotein machinery that reads the genetic code, in the form of messenger RNA (mRNA), to produce proteins. The mechanism of translation is tightly regulated to ensure that cell growth is well sustained. Because of the central role fulfilled by the ribosome, it is not surprising that halting its function can be detrimental and incompatible with life. In bacteria, the ribosome is a major target of inhibitors, as demonstrated by the high number of small molecules identified to bind to it. In eukaryotes, the design of ribosome inhibitors may be used as a therapy to treat cancer cells, which exhibit higher proliferation rates compared to healthy ones. Exciting experimental achievements gathered during the last few years confirmed that the ribosome indeed represents a relevant platform for the development of anticancer drugs. We provide herein an overview of the latest structural data that helped to unveil the molecular bases of inhibition of the eukaryotic ribosome triggered by small molecules.
蛋白质生物合成是所有生命王国的一个重要过程。核糖体是巨大的核糖核蛋白机器，它读取信使核糖核酸（mRNA）形式的遗传密码以产生蛋白质。翻译机制受到严格调控，以确保细胞生长得到良好维持。由于核糖体发挥的核心作用，其功能的停止具有危害性且与生命不相容也就不足为奇了。在细菌中，核糖体是抑制剂的主要作用靶点，这从已鉴定出的大量与之结合的小分子中可见一斑。在真核生物中，核糖体抑制剂的设计可作为一种治疗手段用于治疗癌细胞，与健康细胞相比，癌细胞表现出更高的增殖率。过去几年取得的令人振奋的实验成果证实，核糖体确实是开发抗癌药物的一个重要平台。我们在此概述了最新的结构数据，这些数据有助于揭示小分子引发的对真核核糖体抑制作用的分子基础。
