Cyclin A2 regulates nuclear-envelope breakdown and the nuclear accumulation of cyclin B1
Cyclin A2 regulates nuclear-envelope breakdown and the nuclear accumulation of cyclin B1
复制标题
DOI：
10.1016/j.cub.2006.11.066
复制
发表时间：
2007-01-09
期刊：
影响因子：
9.2
通讯作者：
Ferrell, James E., Jr.
中科院分区：
文献类型：
--
作者：
Gong, Delquin;Pomerening, Joseph R.;Ferrell, James E., Jr.
有丝分裂被认为是由Cdk-细胞周期蛋白复合物的激活触发的[1，2]。在这里，我们已经使用RNA干扰（RNAi），以评估三个有丝分裂细胞周期蛋白，细胞周期蛋白A2，B1和B2，在HeLa细胞的中心体分离和核膜破裂（NEB）的调节中的作用。我们发现，NEB的时间影响很小，敲低细胞周期蛋白B1和B2单独或组合。然而，敲低细胞周期蛋白A2明显延迟NEB，敲低细胞周期蛋白A2和B1进一步延迟NEB。在细胞周期蛋白A2敲低的细胞中，细胞周期蛋白B1-Cdk 1激活的时间是正常的，中心体分离没有延迟，这一事件显然是由细胞质细胞周期蛋白B1-Cdk 1的激活控制的[3]。然而，细胞周期蛋白B1-Cdk 1的核积累显着延迟在细胞周期蛋白A2敲低细胞。最后，一个组成性核细胞周期蛋白B1，但不是野生型细胞周期蛋白B1，恢复正常NEB的时间在细胞周期蛋白A2敲低细胞。这些发现表明，细胞周期蛋白A2是需要及时NEB，而细胞周期蛋白B1和B2不是。然而，细胞周期蛋白B1易位到细胞核之前，NEB在细胞周期蛋白A2依赖的方式，并能够支持NEB，如果使组成性核。
Mitosis is thought to be triggered by the activation of Cdk-cyclin complexes [1, 2]. Here we have used RNA interference (RNAi) to assess the roles of three mitotic cyclins, cyclins A2, B1, and B2, in the regulation of centrosome separation and nuclear-envelope breakdown (NEB) in HeLa cells. We found that the timing of NEB was affected very little by knocking down cyclins B1 and B2 alone or in combination. However, knocking down cyclin A2 markedly delayed NEB, and knocking down both cyclins A2 and B1 delayed NEB further. The timing of cyclin B1-Cdk1 activation was normal in cyclin A2 knockdown cells, and there was no delay in centrosome separation, an event apparently controlled by the activation of cytoplasmic cyclin B1-Cdk1 [3]. However, nuclear accumulation of cyclin B1-Cdk1 was markedly delayed in cyclin A2 knockdown cells. Finally, a constitutively nuclear cyclin B1, but not wild-type cyclin B1, restored normal NEB timing in cyclin A2 knockdown cells. These findings show that cyclin A2 is required for timely NEB, whereas cyclins B1 and B2 are not. Nevertheless cyclin B1 translocates to the nucleus just prior to NEB in a cyclin A2-dependent fashion and is capable of supporting NEB if rendered constitutively nuclear.