The importance of ribosome production, and the 5S RNP-MDM2 pathway, in health and disease.
The importance of ribosome production, and the 5S RNP-MDM2 pathway, in health and disease.
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DOI：
10.1042/bst20160106
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发表时间：
2016-08-15
影响因子：
3.9
通讯作者：
Watkins NJ
中科院分区：
文献类型：
--
作者：
Pelava A;Schneider C;Watkins NJ
核糖体是丰富的大RNA-蛋白质复合物，是细胞中所有蛋白质合成的来源。核糖体的产生是一个极其消耗能量的细胞过程，长期以来一直与人类健康和疾病有关。最近，已经表明核糖体生物合成与多种细胞信号传导途径密切相关，并且核糖体产生中的缺陷可以导致多种人类疾病。此外，响应饮食中营养水平的核糖体产生的变化导致肝脏的代谢重新编程。响应于细胞应激的核糖体产生减少或异常或编码对核糖体生物发生至关重要的因子的基因突变导致肿瘤抑制因子p53的激活，这导致细胞转录的重编程。核糖体组装中间体5S RNP（核糖核蛋白颗粒），含有RPL 5，RPL 11和5S rRNA，当核糖体生物合成被阻断时积累。过量的5S RNP与细胞中主要的p53抑制因子鼠双微体2（MDM 2）结合，抑制其功能并导致p53活化。在这里，我们讨论了参与核糖体生物合成的细胞和人类健康和疾病中的p53的稳态。
Ribosomes are abundant, large RNA–protein complexes that are the source of all protein synthesis in the cell. The production of ribosomes is an extremely energetically expensive cellular process that has long been linked to human health and disease. More recently, it has been shown that ribosome biogenesis is intimately linked to multiple cellular signalling pathways and that defects in ribosome production can lead to a wide variety of human diseases. Furthermore, changes in ribosome production in response to nutrient levels in the diet lead to metabolic re-programming of the liver. Reduced or abnormal ribosome production in response to cellular stress or mutations in genes encoding factors critical for ribosome biogenesis causes the activation of the tumour suppressor p53, which leads to re-programming of cellular transcription. The ribosomal assembly intermediate 5S RNP (ribonucleoprotein particle), containing RPL5, RPL11 and the 5S rRNA, accumulates when ribosome biogenesis is blocked. The excess 5S RNP binds to murine double minute 2 (MDM2), the main p53-suppressor in the cell, inhibiting its function and leading to p53 activation. Here, we discuss the involvement of ribosome biogenesis in the homoeostasis of p53 in the cell and in human health and disease.