Jackman M R, Pines J N
Wellcome/CRC Institute of Developmental Biology, Cambridge.
Cancer Surv. 1997;29:47-73.
The entry of a cell into mitosis is regulated by an elaborate network of kinases and phosphatases that control both for the timing of cell division and the complete reorganization of the cellular architecture. The mitotic cyclin/Cdks form part of large multiprotein complexes whose other components are only now beginning to be identified. The continuing identification of proteins that contribute to these complexes and changes in the composition of these complexes are likely to give a more integrated view of how mitotic cyclin/Cdk complexes are regulated and how they function-not only to induce mitosis, but also to aid further mitotic progression. Furthermore, assigning specific G2/M functions to distinct mitotic cyclin/Cdk complexes will require the identification of differences in substrate specificities between the mitotic cyclin/Cdk complexes, perhaps in parallel with specific cyclin knockouts in mice. Such investigations will be complicated by potential functional overlap between mitotic cyclin/Cdk complexes in vitro and in vivo. Although cyclin/Cdk1 is thought to be the major kinase that initiates the onset of mitosis, a more complete understanding of how cells move from G2 to a mitotic state will require further identification of kinases operating upstream, downstream and in parallel with Cdk1, their substrates and their relationship with one another during the G2/M transition.
细胞进入有丝分裂受激酶和磷酸酶构成的精密网络调控，该网络既控制细胞分裂的时间，也控制细胞结构的全面重组。有丝分裂周期蛋白/周期蛋白依赖性激酶（Cdk）是大型多蛋白复合物的一部分，其其他组分直到现在才开始被鉴定。对构成这些复合物的蛋白质的持续鉴定以及这些复合物组成的变化，可能会更全面地了解有丝分裂周期蛋白/Cdk复合物是如何被调控的以及它们如何发挥功能——不仅诱导有丝分裂，还辅助有丝分裂的进一步进程。此外，要将特定的G2/M期功能赋予不同的有丝分裂周期蛋白/Cdk复合物，需要鉴定有丝分裂周期蛋白/Cdk复合物之间底物特异性的差异，可能还需要同时在小鼠中进行特定周期蛋白的基因敲除。有丝分裂周期蛋白/Cdk复合物在体外和体内可能存在功能重叠，这会使此类研究变得复杂。尽管周期蛋白/Cdk1被认为是启动有丝分裂开始的主要激酶，但要更全面地了解细胞如何从G2期进入有丝分裂状态，还需要进一步鉴定在Cdk1上游、下游以及与其平行发挥作用的激酶、它们的底物以及它们在G2/M期转换过程中彼此的关系。
