Cyclin A2 regulates nuclear-envelope breakdown and the nuclear accumulation of cyclin B1

被引:119
作者
Gong, Delquin
Pomerening, Joseph R.
Myers, Jason W.
Gustavsson, Christer
Jones, Joshua T.
Hahn, Angela T.
Meyer, Tobias
Ferrell, James E., Jr.
机构
[1] Stanford Univ, Sch Med, Dept Chem & Syst Biol, CCSR, Stanford, CA 94305 USA
[2] Stanford Univ, Sch Med, Dept Chem & Syst Biol, Clark Ctr, Stanford, CA 94305 USA
[3] Stanford Univ, Sch Med, Dept Cellular & Mol Physiol, Clark Ctr, Stanford, CA 94305 USA
[4] Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA
[5] Stanford Univ, Dept Biol Sci, Stanford, CA 94305 USA
关键词
D O I
10.1016/j.cub.2006.11.066
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页码:85 / 91
页数:7
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