Calcium, calmodulin, and CaMKII requirement for initiation of centrosome duplication in Xenopus egg extracts
Calcium, calmodulin, and CaMKII requirement for initiation of centrosome duplication in Xenopus egg extracts
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DOI：
10.1126/science.1065693
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发表时间：
2002-01-18
期刊：
影响因子：
56.9
通讯作者：
Maller, JL
中科院分区：
文献类型：
--
作者：
Matsumoto, Y;Maller, JL
在许多肿瘤细胞中观察到异常的中心体复制，并可能通过多极有丝分裂纺锤体的形成导致基因组不稳定。周期蛋白依赖性激酶2 （Cdk2）是非洲爪蟾卵提取物中中心体多次复制所必需的，但不是第一轮复制所必需的。鸡蛋提取物的游离钙水平经历周期性振荡。我们在这里表明，鸡蛋提取物中钙的螯合或钙/钙调素依赖性蛋白激酶11 （CaMKII）的特异性失活甚至会阻止初始中心体复制，而Cdk2的失活则不会。通过添加CaMKII和钙调素，可以恢复被抑制提取物的复制。这些结果表明，钙、钙调蛋白和CaMKII是中心体复制起始的必要步骤。我们的数据表明，细胞周期中的钙振荡可能与中心体复制有关。
Aberrant centrosome duplication is observed in many tumor cells and may contribute to genomic instability through the formation of multipolar mitotic spindles. Cyclin-dependent kinase 2 (Cdk2) is required for multiple rounds of centrosome duplication in Xenopus egg extracts but not for the initial round of replication. Egg extracts undergo periodic oscillations in the level of free calcium. We show here that chelation of calcium in egg extracts or specific inactivation of calcium/calmodulin-dependent protein kinase 11 (CaMKII) blocks even initial centrosome duplication, whereas inactivation of Cdk2 does not. Duplication can be restored to inhibited extracts by addition of CaMKII and calmodulin. These results indicate that calcium, calmodulin, and CaMKII are required for an essential step in initiation of centrosome duplication. Our data suggest that calcium oscillations in the cell cycle may be linked to centrosome duplication.