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线粒体核糖体蛋白S18家族:进化史及结肠癌中的Gly132多态性

S18 family of mitochondrial ribosomal proteins: evolutionary history and Gly132 polymorphism in colon carcinoma.

作者信息

Mushtaq Muhammad, Ali Raja Hashim, Kashuba Vladimir, Klein George, Kashuba Elena

机构信息

Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institute, Stockholm, S-17177, Sweden.

KTH Royal Institute of Technology, Science for Life Laboratory, School of Computer Science and Communication, Solna, SE-17 177, Sweden.

出版信息

Oncotarget. 2016 Aug 23;7(34):55649-55662. doi: 10.18632/oncotarget.10957.

Abstract

S18 family of mitochondrial ribosomal proteins (MRPS18, S18) consists of three members, S18-1 to -3. Earlier, we found that overexpression of S18-2 protein resulted in immortalization and eventual transformation of primary rat fibroblasts. The S18-1 and -3 have not exhibited such abilities. To understand the differences in protein properties, the evolutionary history of S18 family was analyzed. The S18-3, followed by S18-1 and S18-2 emerged as a result of ancient gene duplication in the root of eukaryotic species tree, followed by two metazoan-specific gene duplications. However, the most conserved metazoan S18 homolog is the S18-1; it shares the most sequence similarity with S18 proteins of bacteria and of other eukaryotic clades. Evolutionarily conserved residues of S18 proteins were analyzed in various cancers. S18-2 is mutated at a higher rate, compared with S18-1 and -3 proteins. Moreover, the evolutionarily conserved residue, Gly132 of S18-2, shows genetic polymorphism in colon adenocarcinomas that was confirmed by direct DNA sequencing.Concluding, S18 family represents the yet unexplored important mitochondrial ribosomal proteins.

摘要

线粒体核糖体蛋白S18家族(MRPS18,S18)由三个成员组成,即S18-1至-3。此前,我们发现S18-2蛋白的过表达导致原代大鼠成纤维细胞永生化并最终发生转化。而S18-1和-3并未表现出这种能力。为了解蛋白质特性的差异,我们分析了S18家族的进化史。S18-3、其次是S18-1和S18-2是真核生物物种树根中古代基因复制的结果,随后又发生了两次后生动物特有的基因复制。然而,后生动物中最保守的S18同源物是S18-1;它与细菌和其他真核生物分支的S18蛋白具有最高的序列相似性。我们分析了各种癌症中S18蛋白的进化保守残基。与S18-1和-3蛋白相比,S18-2的突变率更高。此外,S18-2的进化保守残基Gly132在结肠腺癌中表现出基因多态性,这一点通过直接DNA测序得到了证实。总之,S18家族代表了尚未被探索的重要线粒体核糖体蛋白。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c0c/5342443/3389f0ca2441/oncotarget-07-55649-g001.jpg

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