Swan Andrew, Barcelo Gail, Schüpbach Trudi
Howard Hughes Medical Institute, Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Development. 2005 Aug;132(16):3669-78. doi: 10.1242/dev.01940. Epub 2005 Jul 20.
Cks is a small highly conserved protein that plays an important role in cell cycle control in different eukaryotes. Cks proteins have been implicated in entry into and exit from mitosis, by promoting Cyclin-dependent kinase (Cdk) activity on mitotic substrates. In yeast, Cks can promote exit from mitosis by transcriptional regulation of cell cycle regulators. Cks proteins have also been found to promote S-phase via an interaction with the SCF(Skp2) Ubiquitination complex. We have characterized the Drosophila Cks gene, Cks30A and we find that it is required for progression through female meiosis and the mitotic divisions of the early embryo through an interaction with Cdk1. Cks30A mutants are compromised for Cyclin A destruction, resulting in an arrest or delay at the metaphase/anaphase transition, both in female meiosis and in the early syncytial embryo. Cks30A appears to regulate Cyclin A levels through the activity of a female germline-specific anaphase-promoting complex, CDC20-Cortex. We also find that a second closely related Cks gene, Cks85A, plays a distinct, non-overlapping role in Drosophila, and the two genes cannot functionally replace each other.
Cks是一种高度保守的小蛋白，在不同真核生物的细胞周期调控中发挥重要作用。Cks蛋白通过促进有丝分裂底物上的细胞周期蛋白依赖性激酶（Cdk）活性，参与有丝分裂的进入和退出。在酵母中，Cks可通过对细胞周期调节因子的转录调控促进有丝分裂的退出。还发现Cks蛋白通过与SCF（Skp2）泛素化复合体相互作用促进S期。我们对果蝇Cks基因Cks30A进行了表征，发现它通过与Cdk1相互作用，参与雌性减数分裂进程以及早期胚胎的有丝分裂，Cks30A突变体中细胞周期蛋白A的降解受损，导致雌性减数分裂和早期合胞体胚胎在中期/后期转换时停滞或延迟。Cks30A似乎通过雌性生殖系特异性后期促进复合体CDC20 - Cortex的活性来调节细胞周期蛋白A的水平。我们还发现，果蝇中另一个与之密切相关的Cks基因Cks85A发挥着独特的、不重叠的作用，这两个基因在功能上不能相互替代。
