Laboratory of Cell Regulation, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, London WC2A 3LY, United Kingdom.
Mol Biol Cell. 2011 Mar 1;22(5):555-69. doi: 10.1091/mbc.E10-07-0644. Epub 2011 Jan 13.
Wee1 is a protein kinase that negatively regulates mitotic entry in G2 phase by suppressing cyclin B-Cdc2 activity, but its spatiotemporal regulations remain to be elucidated. We observe the dynamic behavior of Wee1 in Schizosaccharomyces pombe cells and manipulate its localization and kinase activity to study its function. At late G2, nuclear Wee1 efficiently suppresses cyclin B-Cdc2 around the spindle pole body (SPB). During the G2/M transition when cyclin B-Cdc2 is highly enriched at the SPB, Wee1 temporally accumulates at the nuclear face of the SPB in a cyclin B-Cdc2-dependent manner and locally suppresses both cyclin B-Cdc2 activity and spindle assembly to counteract a Polo kinase-dependent positive feedback loop. Then Wee1 disappears from the SPB during spindle assembly. We propose that regulation of Wee1 localization around the SPB during the G2/M transition is important for proper mitotic entry and progression.
Wee1 是一种蛋白激酶，通过抑制细胞周期蛋白 B-Cdc2 的活性来负调控 G2 期向有丝分裂的进入，但它的时空调节仍有待阐明。我们观察了裂殖酵母细胞中 Wee1 的动态行为，并操纵其定位和激酶活性来研究其功能。在 G2 晚期，核 Wee1 有效地抑制纺锤体极体（SPB）周围的细胞周期蛋白 B-Cdc2。在细胞周期蛋白 B-Cdc2 在 SPB 高度富集的 G2/M 转换期间，Wee1 以细胞周期蛋白 B-Cdc2 依赖性的方式在 SPB 的核面累积，并局部抑制细胞周期蛋白 B-Cdc2 的活性和纺锤体组装，以抵消 Polo 激酶依赖性的正反馈环。然后，在纺锤体组装过程中，Wee1 从 SPB 中消失。我们提出，在 G2/M 转换期间，Wee1 在 SPB 周围的定位调节对于正确的有丝分裂进入和进展非常重要。
