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针对核糖体合成及核仁的抗癌药物研发

Anticancer drug development against ribosome synthesis and the nucleolus.

作者信息

Loiacono Andrew, Huang Sui

机构信息

Department of Cell and Developmental Biology, Northwestern University Feinberg School of Medicine, Chicago, U.S.A.

出版信息

Biochem Soc Trans. 2025 Aug 4. doi: 10.1042/BST20253011.

Abstract

Nucleoli, the most prominent nuclear organelle, form around ribosomal DNA (rDNA) clusters at the p-arms of the five acrocentric chromosomes. Nucleoli are centers of ribosome synthesis, a vital activity in cell proliferation and organism viability. Ribosome biogenesis is a complex process involving the activity of all three RNA polymerases and numerous cellular factors. This energy-consuming process is, therefore, highly regulated, with the transcription of rDNA being the rate-limiting step. Given that uncontrolled cell proliferation is a hallmark of cancer, enhanced ribosome biogenesis plays a crucial role in sustaining tumor growth. In addition, nucleoli are multi-functional organelles, participating in genome organization, cell cycle, stress sensing, macromolecular trafficking, and the sequestration of cellular factors-functions that are also significantly altered in cancerous conditions. This review focuses on summarizing the role of nucleoli in carcinogenesis and anticancer therapeutics that target nucleoli and ribosome synthesis.

摘要

核仁是最显著的核细胞器,在五条近端着丝粒染色体的p臂上围绕核糖体DNA(rDNA)簇形成。核仁是核糖体合成的中心,这是细胞增殖和生物体生存能力中的一项重要活动。核糖体生物发生是一个复杂的过程,涉及所有三种RNA聚合酶的活性和众多细胞因子。因此,这个耗能过程受到高度调控,rDNA的转录是限速步骤。鉴于不受控制的细胞增殖是癌症的一个标志,增强的核糖体生物发生在维持肿瘤生长中起着关键作用。此外,核仁是多功能细胞器,参与基因组组织、细胞周期、应激感应、大分子运输以及细胞因子的隔离——这些功能在癌症状态下也会发生显著改变。本综述着重总结核仁在致癌作用以及靶向核仁和核糖体合成的抗癌治疗中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1c0/12409996/a67e2fda9250/bst-BST20253011-g001.jpg

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