de Las Heras-Rubio A, Perucho L, Paciucci R, Vilardell J, LLeonart M E
Oncology and Pathology Group, Institut de Recerca Hospital Vall d'Hebron, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain.
Cancer Metastasis Rev. 2014 Mar;33(1):115-41. doi: 10.1007/s10555-013-9460-6.
Ribosome biogenesis is the most demanding energetic and metabolic expenditure of the cell. The nucleolus, a nuclear compartment, coordinates rRNA transcription, maturation, and assembly into ribosome subunits. The transcription process is highly coordinated with ribosome biogenesis. In this context, ribosomal proteins (RPs) play a crucial role. In the last decade, an increasing number of studies have associated RPs with extraribosomal functions related to proliferation. Importantly, the expression of RPs appears to be deregulated in several human disorders due, at least in part, to genetic mutations. Although the deregulation of RPs in human malignancies is commonly observed, a more complex mechanism is believed to be involved, favoring the tumorigenic process, its progression and metastasis. This review explores the roles of the most frequently mutated oncogenes and tumor suppressor genes in human cancer that modulate ribosome biogenesis, including their interaction with RPs. In this regard, we propose a new focus for novel therapies.
核糖体生物合成是细胞中能量和代谢消耗最大的过程。核仁作为细胞核的一个区域,协调rRNA的转录、成熟以及组装成核糖体亚基。转录过程与核糖体生物合成高度协调。在这种情况下,核糖体蛋白(RPs)发挥着关键作用。在过去十年中,越来越多的研究将核糖体蛋白与增殖相关的核糖体外功能联系起来。重要的是,核糖体蛋白的表达在一些人类疾病中似乎失调,至少部分原因是基因突变。尽管在人类恶性肿瘤中普遍观察到核糖体蛋白的失调,但人们认为这涉及一种更复杂的机制,这种机制有利于肿瘤发生过程、其进展和转移。本综述探讨了在人类癌症中调节核糖体生物合成的最常见突变癌基因和肿瘤抑制基因的作用,包括它们与核糖体蛋白的相互作用。在这方面,我们提出了新疗法的一个新重点。