Abnormal centrosome amplification in the absence of p53
Abnormal centrosome amplification in the absence of p53
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DOI：
10.1126/science.271.5256.1744
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发表时间：
1996-03-22
期刊：
影响因子：
56.9
通讯作者：
VandeVoude, GF
中科院分区：
文献类型：
--
作者：
Fukasawa, K;Choi, T;VandeVoude, GF
中心体在有丝分裂的保真度中起着至关重要的作用，确保双极纺锤体的建立和染色体的平衡分离。中心体复制在细胞周期中仅发生一次，因此受到高度调节。在这里，它表明，在小鼠胚胎成纤维细胞（MEFs）缺乏p53肿瘤抑制蛋白，多个副本的功能主管中心体在一个细胞周期期间产生。相比之下，从正常小鼠或视网膜母细胞瘤肿瘤抑制基因产物缺陷小鼠制备的MEF不显示这些异常。异常扩增的中心体深刻地影响有丝分裂的保真度，导致染色体的不均等分离。这些观察结果暗示p53在调节中心体复制，并提出一个可能的机制，p53的损失可能会导致遗传不稳定。
The centrosome plays a vital role in mitotic fidelity, ensuring establishment of bipolar spindles and balanced chromosome segregation. Centrosome duplication occurs only once during the cell cycle and is therefore highly regulated. Here, it is shown that in mouse embryonic fibroblasts (MEFs) lacking the p53 tumor suppressor protein, multiple copies of functionally competent centrosomes are generated during a single cell cycle. In contrast, MEFs prepared from normal mice or mice deficient in the retinoblastoma tumor suppressor gene product do not display these abnormalities. The abnormally amplified centrosomes profoundly affect mitotic fidelity, resulting in unequal segregation of chromosomes. These observations implicate p53 in the regulation of centrosome duplication and suggest one possible mechanism by which the loss of p53 may cause genetic instability.