Active cyclin B1-Cdk1 first appears on centrosomes in prophase
Active cyclin B1-Cdk1 first appears on centrosomes in prophase
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DOI：
10.1038/ncb918
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发表时间：
2003-02-01
影响因子：
21.3
通讯作者：
Pines, J
中科院分区：
文献类型：
--
作者：
Jackman, M;Lindon, C;Pines, J
细胞周期蛋白B1-Cdk 1是有丝分裂的关键启动子，但在哺乳动物细胞中何时何地激活尚未精确确定。激活可能发生在细胞核或细胞质中，就在核膜破裂之前，Polo样激酶1（Plk 1）被认为磷酸化细胞周期蛋白B1的核输出序列（内斯），以触发快速核输入。我们提出了磷酸特异性抗体对细胞周期蛋白B1，主要是识别复合物的活性形式。我们发现，细胞周期蛋白B1最初磷酸化的中心体在前期和Plk 1磷酸化细胞周期蛋白B1，但不是在内斯。此外，Plk 1的磷酸化不会导致细胞周期蛋白B1进入细胞核。我们的结论是细胞周期蛋白B1-Cdk 1首先在细胞质中激活，中心体可能作为触发有丝分裂的蛋白质的整合位点。
Cyclin B1-Cdk1 is the key initiator of mitosis, but when and where activation occurs has not been precisely determined in mammalian cells. Activation may occur in the nucleus or cytoplasm, as just before nuclear envelope breakdown, Polo-like kinase1 (Plk1) is proposed to phosphorylate cyclin B1 in its nuclear export sequence (NES), to trigger rapid nuclear import. We raised phosphospecific antibodies against cyclin B1 that primarily recognise the active form of the complex. We show that cyclin B1 is initially phosphorylated on centrosomes in prophase and that Plk1 phosphorylates cyclin B1, but not in the NES. Furthermore, phosphorylation by Plk1 does not cause cyclin B1 to move into the nucleus. We conclude that cyclin B1-Cdk1 is first activated in the cytoplasm and that centrosomes may function as sites of integration for the proteins that trigger mitosis.