de Nooij J C, Letendre M A, Hariharan I K
Massachusetts General Hospital Cancer Center, Charlestown 02129, USA.
Cell. 1996 Dec 27;87(7):1237-47. doi: 10.1016/s0092-8674(00)81819-x.
In a screen for genes that interact with the Rap1 GTPase, we have identified a Drosophila gene, dacapo (dap), which is a member of the p21/p27 family of cdk inhibitors. Unlike mammalian cdk inhibitors studied to date, dap is essential for normal embryonic development. Dacapo inhibits cyclin-cdk activity in vitro. Overexpressing dap during eye development interferes with cell cycle progression and interacts genetically with the retinoblastoma homolog (Rbf) and cyclin E. dap expression in embryos parallels the exit of cells from the cell cycle. dap mutant embryos delay the normal cell cycle exit during development; many cells complete an additional cycle and subsequently become quiescent. Thus, dap functions during embryogenesis to achieve a precisely timed exit from the cell cycle.
在一项针对与Rap1 GTP酶相互作用的基因的筛选中,我们鉴定出一个果蝇基因——dacapo(dap),它是细胞周期蛋白依赖性激酶(cdk)抑制剂的p21/p27家族的成员。与迄今为止研究的哺乳动物cdk抑制剂不同,dap对于正常胚胎发育至关重要。Dacapo在体外抑制细胞周期蛋白-cdk活性。在眼睛发育过程中过表达dap会干扰细胞周期进程,并与视网膜母细胞瘤同源物(Rbf)和细胞周期蛋白E发生遗传相互作用。胚胎中的dap表达与细胞退出细胞周期的过程平行。dap突变胚胎在发育过程中延迟了正常的细胞周期退出;许多细胞完成额外的一个周期,随后进入静止状态。因此,dap在胚胎发生过程中发挥作用,以实现精确的细胞周期退出时间。