Chromosome instability in tumor cells due to defects in Aurora B mediated error correction at kinetochores.
Chromosome instability in tumor cells due to defects in Aurora B mediated error correction at kinetochores.
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DOI：
10.1080/15384101.2018.1553340
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Yen TJ
中科院分区：
文献类型：
--
作者：
Huang H;Lampson M;Efimov A;Yen TJ
我们描述了一组癌细胞的特征，发现它们表现出染色体不稳定性（CIN），这与高频率的异常动粒：微管附着有关。如果不能在分裂后期开始之前解决这些有缺陷的附着，会导致染色体的错误分离。极光B激酶集中在内部着丝粒，在那里它有助于多种动粒功能，其中之一是纠错。对几种CIN细胞系的分析表明，Aurora B激酶功能的许多方面是正常的。此外，极光B激酶的量和活性在检查的CIN细胞的动粒处没有降低。然而，相对于非CIN细胞，OVCAR10、MCF7和U2OS细胞中Aurora B的着丝粒生物传感器的磷酸化持续降低。这表明Aurora B磷酸化对纠错很重要的底物的能力存在局部问题。这种可能性得到了我们通过将内源性Aurora B引导到生物传感器测试的着丝粒区域来改善错误校正和降低CIN细胞中落后染色体频率的能力的支持。我们的研究表明，CIN细胞的动粒有一个缺陷，限制了极光B的基板，是重要的纠错访问。
We characterized a panel of cancer cells and found that they exhibited chromosome instability (CIN) that was associated with high frequencies of aberrant kinetochore:microtubule attachments. Failure to resolve these defective attachments before anaphase onset can lead to missegregation of chromosomes. Aurora B kinase is concentrated at the inner centromere where it contributes to multiple kinetochore functions, one of which is in error-correction. Analysis of several CIN cell lines showed that many aspects of Aurora B kinase functions were normal. Furthermore, the amount and activity of Aurora B kinase was not reduced at the kinetochores of CIN cells that were examined. However, phosphorylation of a centromeric biosensor for Aurora B in OVCAR10, MCF7 and U2OS cells was consistently reduced relative to non CIN cells. This suggested a localized problem with Aurora B’s ability to phosphorylate substrates important for error correction. This possibility was supported by our ability to improve error correction and reduce the frequency of lagging chromosome in CIN cells by directing endogenous Aurora B to the region of centromere that was tested by the biosensor. Our studies suggest that the kinetochores of CIN cells have a defect that limits accessibility of Aurora B to substrates that are important for error-correction.
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影响因子：
21.3
作者：
Bakhoum, Samuel F.;Thompson, Sarah L.;Manning, Amity L.;Compton, Duane A.
通讯作者：
Compton, Duane A.
影响因子：
4
作者：
Cimini, D;Moree, B;Salmon, ED
通讯作者：
Salmon, ED
影响因子：
10.5
作者：
Coschi, Courtney H.;Martens, Alison L.;Dick, Frederick A.
通讯作者：
Dick, Frederick A.
影响因子：
64.8
作者：
Fuller, Brian G.;Lampson, Michael A.;Kapoor, Tarun M.
通讯作者：
Kapoor, Tarun M.
DOI：
10.1073/pnas.89.7.3070
发表时间：
1992-04-01
影响因子：
11.1
作者：
GODWIN, AK;MEISTER, A;ANDERSON, ME
通讯作者：
ANDERSON, ME