Division of Molecular and Cellular Biology, Kobe University Graduate School of Medicine, Kobe, Japan.
Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Cancer Sci. 2023 May;114(5):2078-2086. doi: 10.1111/cas.15755. Epub 2023 Feb 28.
Ribosome biogenesis in the nucleolus is an important process that consumes 80% of a cell's intracellular energy supply. Disruption of this process results in nucleolar stress, triggering the activation of molecular systems that respond to this stress to maintain homeostasis. Although nucleolar stress was originally thought to be caused solely by abnormalities of ribosomal RNA (rRNA) and ribosomal proteins (RPs), an accumulating body of more current evidence suggests that many other factors, including the DNA damage response and oncogenic stress, are also involved in nucleolar stress response signaling. Cells reacting to nucleolar stress undergo cell cycle arrest or programmed death, mainly driven by activation of the tumor suppressor p53. This observation has nominated nucleolar stress as a promising target for cancer therapy. However, paradoxically, some RP mutations have also been implicated in cancer initiation and progression, necessitating caution. In this article, we summarize recent findings on the molecular mechanisms of nucleolar stress and the human ribosomal diseases and cancers that arise in its wake.
核仁中的核糖体生物发生是一个重要的过程，消耗了细胞内能量供应的 80%。该过程的破坏会导致核仁应激，触发分子系统的激活以应对这种应激，从而维持体内平衡。虽然核仁应激最初被认为仅由核糖体 RNA(rRNA)和核糖体蛋白(RPs)的异常引起，但越来越多的现有证据表明，许多其他因素，包括 DNA 损伤反应和致癌应激，也参与了核仁应激反应信号转导。对核仁应激做出反应的细胞会经历细胞周期停滞或程序性死亡，主要是由肿瘤抑制因子 p53 的激活所驱动。这一观察结果将核仁应激作为癌症治疗的一个有前途的靶点。然而，矛盾的是，一些 RP 突变也与癌症的起始和进展有关，因此需要谨慎对待。在本文中，我们总结了核仁应激的分子机制以及由此产生的人类核糖体疾病和癌症的最新发现。
