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

摘要

The events that mark the entry of a cell into mitosis—chromatin condensation, centrosome separation, and nuclear envelope breakdown (NEB)—are thought to be triggered by the activation of Cdk-cyclin complexes [, ]. However, it is not yet clear which complexes are important for which events, or how the various complexes are coordinated. Here we have used RNA interference (RNAi) to assess the roles of three mitotic cyclins, cyclins A2, B1, and B2, 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 []. 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.