Nash R, Tokiwa G, Anand S, Erickson K, Futcher A B
Cold Spring Harbor Laboratory, NY 11724.
EMBO J. 1988 Dec 20;7(13):4335-46. doi: 10.1002/j.1460-2075.1988.tb03332.x.
WHI1-1 is a dominant mutation that reduces cell volume by allowing cells to commit to division at abnormally small sizes, shortening the G1 phase of the cell cycle. The gene was cloned, and dosage studies indicated that the normal gene activated commitment to division in a dose-dependent manner, and that the mutant gene had a hyperactive but qualitatively similar function. Mild over-expression of the mutant gene eliminated G1 phase, apparently entirely relaxing the normal G1 size control, but revealing hitherto cryptic controls. Sequence analysis showed that the hyperactivity of the mutant was caused by the loss of the C-terminal third of the wild-type protein. This portion of the protein contained PEST regions, which may be signals for protein degradation. The WHI1 protein had sequence similarity to clam cyclin A, to sea urchin cyclin and to Schizosaccharomyces pombe cdc13, a cyclin homolog. Since cyclins are inducers of mitosis, WHI1 may be a direct regulator of commitment to division. A probable accessory function of the WHI1 activator is to assist recovery from alpha factor arrest; WHI1-1 mutant cells could not be permanently arrested by pheromone, consistent with a hyperactivation of division.
WHI1-1是一种显性突变,它通过使细胞在异常小的体积时就进入分裂,缩短细胞周期的G1期,从而减小细胞体积。该基因被克隆,剂量研究表明正常基因以剂量依赖的方式激活细胞进入分裂,而突变基因具有过度活跃但性质相似的功能。突变基因的轻度过表达消除了G1期,显然完全放松了正常的G1期大小控制,但揭示了迄今隐藏的控制机制。序列分析表明,突变体的过度活跃是由野生型蛋白C端三分之一的缺失引起的。该蛋白的这一部分包含PEST区域,这可能是蛋白质降解的信号。WHI1蛋白与蛤类细胞周期蛋白A、海胆细胞周期蛋白以及粟酒裂殖酵母的细胞周期蛋白同源物cdc13具有序列相似性。由于细胞周期蛋白是有丝分裂的诱导剂,因此WHI1可能是细胞进入分裂的直接调节因子。WHI1激活剂的一个可能的辅助功能是协助从α因子阻滞中恢复;WHI1-1突变细胞不能被信息素永久阻滞,这与分裂的过度激活一致。