Prober D A, Edgar B A
Molecular and Cellular Biology Program, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Cell. 2000 Feb 18;100(4):435-46. doi: 10.1016/s0092-8674(00)80679-0.
The Ras GTPase links extracellular mitogens to intracellular mechanisms that control cell proliferation. To understand how Ras regulates proliferation in vivo, we activated or inactivated Ras in cell clones in the developing Drosophila wing. Cells lacking Ras were smaller, had reduced growth rates, accumulated in G1, and underwent apoptosis due to cell competition. Conversely, activation of Ras increased cell size and growth rates and promoted G1/S transitions. Ras upregulated the growth driver dMyc, and both Ras and dMyc increased levels of cyclin E posttranscriptionally. We propose that Ras primarily promotes growth and that growth is coupled to G1/S progression via cyclin E. Interestingly, upregulation of growth by Ras did not deregulate G2/M progression or a developmentally regulated cell cycle exit.
Ras小GTP酶将细胞外有丝分裂原与控制细胞增殖的细胞内机制联系起来。为了了解Ras在体内如何调节增殖,我们在发育中的果蝇翅膀的细胞克隆中激活或失活了Ras。缺乏Ras的细胞较小,生长速率降低,在G1期积累,并由于细胞竞争而发生凋亡。相反,Ras的激活增加了细胞大小和生长速率,并促进了G1/S期转换。Ras上调了生长驱动因子dMyc,并且Ras和dMyc都在转录后增加了细胞周期蛋白E的水平。我们提出,Ras主要促进生长,并且生长通过细胞周期蛋白E与G1/S期进程相关联。有趣的是,Ras介导的生长上调并未解除对G2/M期进程或发育调控的细胞周期退出的调节。