Ribosomal proteins and human diseases: pathogenesis, molecular mechanisms, and therapeutic implications.
Ribosomal proteins and human diseases: pathogenesis, molecular mechanisms, and therapeutic implications.
复制标题
核糖体蛋白质和人类疾病：发病机理，分子机制和治疗意义。
DOI：
10.1002/med.21327
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发表时间：
2015-03
影响因子：
13.3
通讯作者：
Zhang R
中科院分区：
文献类型：
--
作者：
Wang W;Nag S;Zhang X;Wang MH;Wang H;Zhou J;Zhang R
核糖体是蛋白质合成机器的重要组成部分。核糖体生物发生过程组织良好且受到严格调控。最近的研究表明，核糖体蛋白（RP）具有核糖体外功能，参与细胞增殖、分化、凋亡、DNA修复和其他细胞过程。 RP 的功能障碍与血液、代谢、心血管疾病和癌症的发生和进展有关。核糖体生物发生的扰动会导致核糖体应激，从而通过 RPs-MDM2 相互作用触发 p53 信号通路的激活，从而导致 p53 依赖性细胞周期停滞和凋亡。 RP 还通过 p53 独立机制调节细胞功能。我们在此回顾了 RP 研究几个前沿的最新进展，包括了解它们的生物学特征和在调节细胞功能、维持细胞稳态中的作用，以及它们在人类疾病发病机制中的作用。我们还强调了这项研究在识别分子生物标志物以及发现和开发人类疾病新疗法方面的转化潜力。
Ribosomes are essential components of the protein synthesis machinery. The process of ribosome biogenesis is well organized and tightly regulated. Recent studies have shown that ribosomal proteins (RPs) have extraribosomal functions that are involved in cell proliferation, differentiation, apoptosis, DNA repair, and other cellular processes. The dysfunction of RPs has been linked to the development and progression of hematological, metabolic, and cardiovascular diseases and cancer. Perturbation of ribosome biogenesis results in ribosomal stress, which triggers activation of the p53 signaling pathway through RPs-MDM2 interactions, resulting in p53-dependent cell cycle arrest and apoptosis. RPs also regulate cellular functions through p53-independent mechanisms. We herein review the recent advances in several forefronts of RP research, including the understanding of their biological features and roles in regulating cellular functions, maintaining cell homeostasis, and their involvement in the pathogenesis of human diseases. We also highlight the translational potential of this research for the identification of molecular biomarkers, and in the discovery and development of novel treatments for human diseases.