Singh P, Wong S H, Hong W
Membrane Biology Laboratory, National University of Singapore.
EMBO J. 1994 Jul 15;13(14):3329-38. doi: 10.1002/j.1460-2075.1994.tb06635.x.
The transcription factor E2F has been implicated in controlling the activation of multiple genes associated with cell proliferation. E2F-1, which is a component of E2F, can promote oncogenesis when transfected into REF cells. The transformation caused by E2F-1 correlates with constitutive overexpression of the transgene, increased transcription of E2F-dependent genes and the enhancement of two E2F DNA binding complexes containing the retinoblastoma susceptibility gene product (Rb) and E2F-1. The oncogenic potential of E2F-1 is dependent on functional DNA binding and transactivation domains but does not require the ability to interact directly with Rb. These findings provide the first direct evidence that sustained unregulated expression of E2F-1 can lead to the loss of cell proliferation control and that E2F-1 is a key component in cell cycle control.
转录因子E2F已被证实参与调控多个与细胞增殖相关基因的激活。E2F的一个组成部分E2F-1，转染到REF细胞中时可促进肿瘤发生。E2F-1引起的转化与转基因的组成型过表达、E2F依赖基因转录增加以及两种含有视网膜母细胞瘤易感基因产物（Rb）和E2F-1的E2F DNA结合复合物增强有关。E2F-1的致癌潜力取决于功能性DNA结合和反式激活结构域，但不需要直接与Rb相互作用的能力。这些发现首次直接证明，E2F-1持续不受调控的表达可导致细胞增殖控制丧失，且E2F-1是细胞周期调控的关键组成部分。
