Frontier Science Research Center, University of Miyazaki, Miyazaki, Japan.
Wiley Interdiscip Rev RNA. 2011 Jul-Aug;2(4):507-22. doi: 10.1002/wrna.73. Epub 2011 Jan 20.
Ribosomes, the molecular factories that carry out protein synthesis, are essential for every living cell. Ribosome biogenesis, the process of ribosome synthesis, is highly complex and energy consuming. Over the last decade, many exciting and novel findings have linked various aspects of ribosome biogenesis to cell growth and cell cycle control. Defects in ribosome biogenesis have also been linked to human diseases. It is now clear that disruption of ribosome biogenesis causes nucleolar stress that triggers a p53 signaling pathway, thus providing cells with a surveillance mechanism for monitoring ribosomal integrity. Although the exact mechanisms of p53 induction in response to nucleolar stress are still unknown, several ribosomal proteins have been identified as key players in this ribosome-p53 signaling pathway. Recent studies of human ribosomal pathologies in a variety of animal models have also highlighted the role of this pathway in the pathophysiology of these diseases. However, it remains to be understood why the effect of ribosomal malfunction is not a universal response in all cell types but is restricted to particular tissues, causing the specific phenotypes seen in ribosomal diseases. A challenge for future studies will be to identify additional players in this signaling pathway and to elucidate the underlying molecular mechanisms that link defective ribosome synthesis to p53.
核糖体是执行蛋白质合成的分子工厂，对所有活细胞都是必不可少的。核糖体生物发生是核糖体合成的过程，非常复杂且耗能。在过去的十年中，许多令人兴奋和新颖的发现将核糖体生物发生的各个方面与细胞生长和细胞周期控制联系起来。核糖体生物发生的缺陷也与人类疾病有关。现在很清楚，核糖体生物发生的破坏会引起核仁应激，从而触发 p53 信号通路，从而为细胞提供一种监测核糖体完整性的监控机制。尽管 p53 诱导对核仁应激的具体机制尚不清楚，但已鉴定出几种核糖体蛋白作为该核糖体-p53 信号通路中的关键参与者。最近在各种动物模型中对人类核糖体病理学的研究也强调了该途径在这些疾病的病理生理学中的作用。然而，尚不清楚为什么核糖体功能障碍的影响不是所有细胞类型的普遍反应，而是仅限于特定组织，导致在核糖体疾病中观察到特定的表型。未来研究的一个挑战将是确定该信号通路中的其他参与者，并阐明将缺陷核糖体合成与 p53 联系起来的潜在分子机制。
