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中心体与疾病:为何同曲异调?

Centrosomes in disease: how the same music can sound so different?

机构信息

Department of Translational Research, Institut Curie, PSL University, 26 rue d' Ulm, F-75248 Paris Cedex 05, France.

Biology of Centrosomes and Genetic Instability Lab, CNRS, Institut Curie, PSL Research University, UMR144, 12 rue Lhomond, 75005 Paris, France.

出版信息

Curr Opin Struct Biol. 2021 Feb;66:74-82. doi: 10.1016/j.sbi.2020.09.011. Epub 2020 Nov 10.

Abstract

Centrosomes are the major microtubule organizing center of animal cells. Centrosomes contribute to timely bipolar spindle assembly during mitosis and participate in the regulation of other processes such as polarity establishment and cell migration. Centrosome numbers are tightly controlled during the cell cycle to ensure that mitosis is initiated with only two centrosomes. Deviations in centrosome number or structure are known to impact cell or tissue homeostasis and can impact different processes as diverse as proliferation, death or disease. Interestingly, defects in centrosome number seem to culminate with common responses, which depend on p53 activation even in different contexts such as development or cancer. p53 is a tumor suppressor gene with essential roles in the maintenance of genetic stability normally stimulated by various cellular stresses. Here, we review current knowledge and discuss how defects in centrosome structure and number can lead to different human pathologies.

摘要

中心体是动物细胞的主要微管组织中心。中心体有助于有丝分裂期间及时形成两极纺锤体,并参与调节其他过程,如极性建立和细胞迁移。在细胞周期中,中心体的数量受到严格控制,以确保只有两个中心体才能启动有丝分裂。中心体数量或结构的偏差已知会影响细胞或组织的稳态,并可能影响增殖、死亡或疾病等不同过程。有趣的是,中心体数量的缺陷似乎最终会导致共同的反应,即使在不同的环境中,如发育或癌症,也依赖于 p53 的激活。p53 是一种肿瘤抑制基因,在维持遗传稳定性方面具有重要作用,通常受到各种细胞应激的刺激。在这里,我们回顾了当前的知识,并讨论了中心体结构和数量的缺陷如何导致不同的人类病理。

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