Cyclin-dependent kinase 2 (Cdk2) is required for centrosome duplication in mammalian cells
Cyclin-dependent kinase 2 (Cdk2) is required for centrosome duplication in mammalian cells
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DOI：
10.1016/s0960-9822(99)80191-2
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发表时间：
1999-04-22
期刊：
影响因子：
9.2
通讯作者：
Nishida, E
中科院分区：
文献类型：
--
作者：
Matsumoto, Y;Hayashi, K;Nishida, E
中心体复制是形成双极有丝分裂纺锤体所必需的。令人惊讶的是，即使DNA复制或有丝分裂被抑制，中心体复制仍然可以发生[1-5]。因此，它仍然是未知的中心体复制是如何协调与细胞周期。在这里，我们表明，中心体复制需要细胞周期蛋白依赖性激酶2（Cdk 2）在哺乳动物细胞。我们已经发现，在中国仓鼠卵巢（CHO）细胞，而中心体复制是不受抑制的羟基脲（HU）的治疗，这逮捕了细胞在S期，它是抑制含羞草碱治疗，这逮捕了细胞在G1期晚期。Cdk 2活性在HU处理的细胞中高于在含羞草碱处理的细胞中。值得注意的是，用丁内酯I或roscovitine [6]或通过Cdk抑制剂p21（Waf 1/Cip 1）的表达抑制HU处理的细胞中的Cdk 2活性，阻断了持续的中心体复制。此外，Cdk 2的过表达逆转了含羞草碱处理对中心体复制的抑制。这些结果表明，Cdk 2活性的中心体复制的要求，因此建议一个潜在的中心体复制与细胞周期的协调机制。
Centrosome duplication is indispensable for the formation of the bipolar mitotic spindle. Surprisingly, even if DNA replication or;mitosis is inhibited, centrosome duplication can Still occur [1-5]. Thus, it remains unknown how centrosome duplication is coordinated with the cell cycle. Here, we show that centrosome duplication requires cyclin-dependent: kinase 2 (Cdk2) in mammalian cells. We have found that in Chinese hamster ovary (CHO) cells, whereas centrosome duplication is not inhibited by hydroxyurea (HU) treatment, which arrests the cells in S phase, it is inhibited by mimosine treatment, which arrests the cells in late G1 phase. Cdk2 activity was higher in HU-treated cells than in mimosine-treated cells. Remarkably, inhibition of the Cdk2 activity in HU-treated cells with butyrolactone I or roscovitine [6], or by expression of the Cdk inhibitor p21(Waf1/Cip1), blocked the continued centrosome duplication. Moreover, overexpression of Cdk2 reversed the inhibition of centrosome duplication by mimosine treatment. These results indicate a requirement of Cdk2 activity for centrosome duplication and therefore suggest an underlying mechanism for the coordination of centrosome duplication with the cell cycle.