Mushtaq Muhammad, Ali Raja Hashim, Kashuba Vladimir, Klein George, Kashuba Elena
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.
Oncotarget. 2016 Aug 23;7(34):55649-55662. doi: 10.18632/oncotarget.10957.
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.
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。