Pk Sreepriya, Freimanis Joshua, Kovala Thomas, Parissenti Amadeo M
Ph.D. Program in Biomolecular Sciences, Laurentian University, Sudbury, ON P3E 2C6, Canada.
Biomedical Biology Program, School of Natural Sciences, Laurentian University, Sudbury, ON P3E 2C6, Canada.
Cancers (Basel). 2025 Aug 29;17(17):2825. doi: 10.3390/cancers17172825.
Protein translation by ribosomes is one of the most energetically costly cellular processes. Consequently, the number and activity of ribosomes in cells and tissues are precisely tailored to match metabolic demands. While ribosomal proteins (RPs) play essential roles in facilitating and regulating the translation of mRNA transcripts into protein, there is increasing evidence that free RPs not bound to ribosomes can play important roles in cellular regulation. Often, free RPs act as tumour suppressors by multiple mechanisms, for example, by inducing cell cycle arrest through their ability to bind and inhibit MDM2-mediated p53 degradation. Dysregulation of these RPs, however, can result in various diseases like Diamond-Blackfan anemia, ribosomopathies, and other diseases. In cancer, epigenetic modifications, altered transcription, and processing defects in the rRNAs create "onco-ribosomes" that strongly support tumour cell replication, invasion and metastasis. In this context, free RPs in tumour cells (often mutated or post-translationally modified) further promote tumour cell proliferation, invasion, and metastasis. This review focuses specifically on extra-ribosomal roles for RPs, where depending upon cellular context, they act outside of the ribosome to either suppress tumorigenesis in normal tissues or promote tumour proliferation and progression. This new understanding of the interplay between RPs and pathways suppressing or promoting tumorigenesis further emphasizes why the ribosome is increasingly being seen as an important therapeutic target in human cancers.
核糖体进行的蛋白质翻译是细胞中能量消耗最高的过程之一。因此，细胞和组织中核糖体的数量和活性经过精确调整，以匹配代谢需求。虽然核糖体蛋白（RPs）在促进和调节mRNA转录本翻译成蛋白质的过程中发挥着重要作用，但越来越多的证据表明，未与核糖体结合的游离核糖体蛋白在细胞调节中也能发挥重要作用。通常，游离核糖体蛋白通过多种机制发挥肿瘤抑制作用，例如，通过结合并抑制MDM2介导的p53降解来诱导细胞周期停滞。然而，这些核糖体蛋白的失调可能导致多种疾病，如先天性纯红细胞再生障碍性贫血、核糖体病和其他疾病。在癌症中，rRNA的表观遗传修饰、转录改变和加工缺陷会产生“致癌核糖体”，有力地支持肿瘤细胞的复制、侵袭和转移。在这种情况下，肿瘤细胞中的游离核糖体蛋白（通常发生突变或翻译后修饰）会进一步促进肿瘤细胞的增殖、侵袭和转移。本综述特别关注核糖体蛋白在核糖体之外的作用，根据细胞环境的不同，它们在核糖体之外发挥作用，要么抑制正常组织中的肿瘤发生，要么促进肿瘤的增殖和进展。对核糖体蛋白与抑制或促进肿瘤发生的信号通路之间相互作用的这一新认识，进一步强调了为什么核糖体越来越被视为人类癌症的重要治疗靶点。
