Cyclin-dependent kinase 2 is dispensable for normal centrosome duplication but required for oncogene-induced centrosome overduplication
Cyclin-dependent kinase 2 is dispensable for normal centrosome duplication but required for oncogene-induced centrosome overduplication
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DOI：
10.1038/sj.onc.1209310
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发表时间：
2006-05-01
期刊：
影响因子：
8
通讯作者：
Duensing, S.
中科院分区：
文献类型：
--
作者：
Duensing, A.;Liu, Y.;Duensing, S.
细胞周期蛋白依赖性激酶2 （CDK2）被认为是中心体复制的主要调控因子。使用小鼠胚胎。在Cdk2基因缺失的成母细胞（mef）中，我们发现Cdk2对于正常的中心体复制、成熟和双极有丝分裂纺锤体形成是不需要的。相反，Cdk2缺乏完全消除了由病毒致癌基因诱导的异常中心体复制。从机制上讲，Cdk2野生型mef中的中心体过度复制涉及到多余的未成熟中心体的形成。这些结果表明，正常和异常的中心体复制对CDK2活性的要求有显著不同，并指出CDK2在中心体进行异常复制的许可中起作用。此外，我们的研究结果表明，CDK2可能是抑制中心体介导的肿瘤细胞染色体不稳定性的合适治疗靶点。
Cyclin- dependent kinase 2 ( CDK2) has been proposed to function as a master regulator of centrosome duplication. Using mouse embryonic. broblasts ( MEFs) in which Cdk2 has been genetically deleted, we show here that CDK2 is not required for normal centrosome duplication, maturation and bipolar mitotic spindle formation. In contrast, Cdk2 deficiency completely abrogates aberrant centrosome duplication induced by a viral oncogene. Mechanistically, centrosome overduplication in MEFs wild- type for Cdk2 involves the formation of supernumerary immature centrosomes. These results indicate that normal and abnormal centrosome duplication have significantly different requirements for CDK2 activity and point to a role of CDK2 in licensing centrosomes for aberrant duplication. Furthermore, our findings suggest that CDK2 may be a suitable therapeutic target to inhibit centrosome- mediated chromosomal instability in tumor cells.