Datar Sanjeev A, Galloni Mireille, de la Cruz Aida, Marti Mark, Edgar Bruce A, Frei Christian
Fred Hutchinson Cancer Research Center, Division of Basic Sciences, Seattle, Washington, USA.
Cell Cycle. 2006 Mar;5(6):647-52. Epub 2006 Mar 15.
The Drosophila melanogaster cyclin dependent protein kinase complex CycD/Cdk4 has been shown to regulate cellular growth (accumulation of mass) as well as proliferation (cell cycle progression). In contrast, the orthologous mammalian complex has been shown to regulate cell cycle progression, but possible functions in growth control have not been addressed directly. To test whether mammalian Cyclin D1/Cdk4 complexes are capable of driving cell growth, we expressed such a complex in Drosophila. Using assays that distinguish between mass increase and cell cycle progression, we found that this complex stimulated cell growth, like its Drosophila counterpart. Furthermore, Hif-1 prolyl hydroxylase (Hph) is required for both complexes to drive growth. Our data suggest that the growth-specific function of CycD/Cdk4 is conserved from arthropods to mammals.
黑腹果蝇细胞周期蛋白依赖性蛋白激酶复合物CycD/Cdk4已被证明可调节细胞生长(质量积累)以及增殖(细胞周期进程)。相比之下,直系同源的哺乳动物复合物已被证明可调节细胞周期进程,但在生长控制方面的可能功能尚未得到直接研究。为了测试哺乳动物细胞周期蛋白D1/Cdk4复合物是否能够驱动细胞生长,我们在果蝇中表达了这样一种复合物。使用区分质量增加和细胞周期进程的检测方法,我们发现这种复合物像其果蝇对应物一样刺激细胞生长。此外,两种复合物驱动生长都需要缺氧诱导因子-1脯氨酰羟化酶(Hph)。我们的数据表明,CycD/Cdk4的生长特异性功能从节肢动物到哺乳动物是保守的。