Cdc25B cooperates with Cdc25A to induce mitosis but has a unique role in activating cyclin B1-Cdk1 at the centrosome.

Cdc25B cooperates with Cdc25A to induce mitosis but has a unique role in activating cyclin B1-Cdk1 at the centrosome.
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CDC25B与CDC25A合作以诱导有丝分裂,但在激活中心体的细胞周期蛋白B1-CDK1方面具有独特的作用。

DOI:
10.1083/jcb.200503066
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发表时间:
2005-10-10
影响因子:
7.8
通讯作者:
Rosenthal, Christina Karlsson
Rosenthal, Christina Karlsson
中科院分区:
生物学1区
文献类型:
--
作者:
Lindqvist, Arne;Kallstrom, Helena;Lundgren, Andreas;Barsoum, Emad;Rosenthal, Christina Karlsson

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Cdc 25磷酸酶是激活有丝分裂细胞周期蛋白Cdks所必需的,但三种哺乳动物亚型(A,B和C)的确切作用尚不清楚。使用RNA干扰减少HeLa和HEK 293细胞中每个Cdc 25亚型的表达,我们观察到Cdc 25 A和-B都需要有丝分裂进入,而Cdc 25 C单独不能诱导有丝分裂。我们发现,小干扰RNA对Cdc 25 A或-B的G2延迟伴随着细胞周期蛋白B1-Cdk 1和细胞周期蛋白A-Cdk 2复合物的活性降低和细胞周期蛋白B1蛋白的积累延迟。此外,三维延时显微镜和定量Cdk 1磷酸化与细胞周期蛋白B1水平在个别细胞中显示,Cdc 25 A和-B发挥特定的功能,在有丝分裂的启动:Cdc 25 A可能发挥作用,在染色质凝聚,而Cdc 25 B特异性激活中心体上的细胞周期蛋白B1-Cdk 1。
Cdc25 phosphatases are essential for the activation of mitotic cyclin–Cdks, but the precise roles of the three mammalian isoforms (A, B, and C) are unclear. Using RNA interference to reduce the expression of each Cdc25 isoform in HeLa and HEK293 cells, we observed that Cdc25A and -B are both needed for mitotic entry, whereas Cdc25C alone cannot induce mitosis. We found that the G2 delay caused by small interfering RNA to Cdc25A or -B was accompanied by reduced activities of both cyclin B1–Cdk1 and cyclin A–Cdk2 complexes and a delayed accumulation of cyclin B1 protein. Further, three-dimensional time-lapse microscopy and quantification of Cdk1 phosphorylation versus cyclin B1 levels in individual cells revealed that Cdc25A and -B exert specific functions in the initiation of mitosis: Cdc25A may play a role in chromatin condensation, whereas Cdc25B specifically activates cyclin B1–Cdk1 on centrosomes.