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[作为细胞衰老调节因子的核仁]

[The nucleolus as a regulator of cellular senescence].

作者信息

Rosete Maria, Padros Maria Rosa, Vindrola Osvaldo

机构信息

Laboratorio de Bioquímica Celular, Instituto de Fisiología. Benemérita Universidad Autónoma de Puebla, Puebla, México.

出版信息

Medicina (B Aires). 2007;67(2):183-94.

PMID:17593607
Abstract

The nucleolus has been considered originally only as the site for the ribosome synthesis, but now it is well known that it represents a dynamic nuclear structure involved in important cellular processes. Several evidences have demonstrated that the nucleolus regulates the cellular senescence. Specific mutations on the DNAs codifying for nucleolar proteins induced premature senescence from yeast to human. The failure to repress the genes transcription codifying for damaged rRNA, and the mutations in DNA helicases, which minimizes the formation of DNA extra-chromosomal circles codifying for rRNA, modify the nucleolar structure and induce premature senescence in yeast. Similarly, in humans, the reduction of these DNA helicases levels, which are localized in the nucleoli and participate in maintenance of genomic integrity, helps to the development of those diseases associated with premature senescence. Furthermore, the presence in the nucleolus of some telomerase components, indicates that part of the biosynthesis of this enzyme occurred in this nuclear structure; suggesting a communication between the nucleolus and the synthesis of the telomeres in the regulation of cell senescence. On the other hand, the nucleolus sequesters proteins to regulate its own biological activity, from the start to the end of cellular replication. In addition this nuclear structure is involved in the biosynthesis of most cellular ribonucleoprotein particles, as well as in cell cycle regulation, making it central to gene expression. In conclusion, the nucleolus became a multifunctional subnuclear structure involved from cell proliferation to cell senescence.

摘要

核仁最初仅被认为是核糖体合成的场所,但现在众所周知,它是一种动态的核结构,参与重要的细胞过程。多项证据表明,核仁调节细胞衰老。编码核仁蛋白的DNA上的特定突变会导致从酵母到人类的早衰。无法抑制编码受损rRNA的基因转录,以及DNA解旋酶的突变(这会使编码rRNA的DNA染色体外环状结构的形成减至最少),会改变核仁结构并在酵母中诱导早衰。同样,在人类中,这些位于核仁且参与基因组完整性维持的DNA解旋酶水平的降低,会促使与早衰相关的疾病发展。此外,核仁中存在一些端粒酶成分,这表明该酶的部分生物合成发生在这个核结构中;这暗示了在细胞衰老调控中核仁与端粒合成之间存在联系。另一方面,从细胞复制开始到结束,核仁隔离蛋白质以调节其自身的生物学活性。此外,这个核结构参与大多数细胞核糖核蛋白颗粒的生物合成以及细胞周期调控,使其成为基因表达的核心。总之,核仁成为了一个从细胞增殖到细胞衰老都涉及的多功能亚核结构。

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