Harvey Stacy L, Charlet Alyson, Haas Wilhelm, Gygi Steven P, Kellogg Douglas R
Department of Molecular, Cell, and Developmental Biology, University of California Santa Cruz, Santa Cruz, California 95064, USA.
Cell. 2005 Aug 12;122(3):407-20. doi: 10.1016/j.cell.2005.05.029.
The Wee1 kinase phosphorylates and inhibits cyclin-dependent kinase 1 (Cdk1), thereby delaying entry into mitosis until appropriate conditions have been met. An understanding of the mechanisms that regulate Wee1 should provide new insight into how cells make the decision to enter mitosis. We report here that Swe1, the budding-yeast homolog of Wee1, is directly regulated by Cdk1. Phosphorylation of Swe1 by Cdk1 activates Swe1 and is required for formation of a stable Swe1-Cdk1 complex that maintains Cdk1 in the inhibited state. Dephosphorylation of Cdk1 leads to further phosphorylation of Swe1 and release of Cdk1. Thus, Cdk1 both positively and negatively regulates its own inhibitor. Regulation of the Swe1-Cdk1 complex is likely to play a critical role in controlling the transition into mitosis.
Wee1激酶使细胞周期蛋白依赖性激酶1（Cdk1）磷酸化并抑制其活性，从而将有丝分裂的进入延迟到合适的条件满足之时。了解调控Wee1的机制应该能为细胞如何决定进入有丝分裂提供新的见解。我们在此报告，Wee1在芽殖酵母中的同源物Swe1直接受Cdk1调控。Cdk1对Swe1的磷酸化激活了Swe1，并且是形成稳定的Swe1-Cdk1复合物所必需的，该复合物使Cdk1维持在抑制状态。Cdk1的去磷酸化导致Swe1的进一步磷酸化以及Cdk1的释放。因此，Cdk1对其自身的抑制剂既有正向调节作用，也有负向调节作用。Swe1-Cdk1复合物的调控可能在控制向有丝分裂的转变中起关键作用。
