Gaubatz S, Lindeman G J, Ishida S, Jakoi L, Nevins J R, Livingston D M, Rempel R E
The Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA.
Mol Cell. 2000 Sep;6(3):729-35. doi: 10.1016/s1097-2765(00)00071-x.
E2F transcription factors are major regulators of cell proliferation. The diversity of the E2F family suggests that individual members perform distinct functions in cell cycle control. E2F4 and E2F5 constitute a defined subset of the family. Until now, there has been little understanding of their individual biochemical and biological functions. Here, we report that simultaneous inactivation of E2F4 and E2F5 in mice results in neonatal lethality, suggesting that they perform overlapping functions during mouse development. Embryonic fibroblasts isolated from these mice proliferated normally and reentered from Go with normal kinetics compared to wild-type cells. However, they failed to arrest in G1 in response to p16INK4a. Thus, E2F4 and E2F5 are dispensable for cell cycle progression but necessary for pocket protein-mediated G1 arrest of cycling cells.
E2F转录因子是细胞增殖的主要调节因子。E2F家族的多样性表明其各个成员在细胞周期调控中发挥着不同的功能。E2F4和E2F5构成了该家族中一个特定的亚群。到目前为止，人们对它们各自的生化和生物学功能了解甚少。在此，我们报告在小鼠中同时失活E2F4和E2F5会导致新生小鼠死亡，这表明它们在小鼠发育过程中发挥着重叠的功能。与野生型细胞相比，从这些小鼠分离出的胚胎成纤维细胞正常增殖，并以正常动力学从G0期重新进入细胞周期。然而，它们在受到p16INK4a刺激时无法在G1期停滞。因此，E2F4和E2F5对于细胞周期进程并非必需，但对于口袋蛋白介导的循环细胞G1期停滞是必需的。
