Hijmans E M, Voorhoeve P M, Beijersbergen R L, van 't Veer L J, Bernards R
Division of Molecular Carcinogenesis, Netherlands Cancer Institute, Amsterdam.
Mol Cell Biol. 1995 Jun;15(6):3082-9. doi: 10.1128/MCB.15.6.3082.
E2F DNA binding sites are found in a number of genes whose expression is tightly regulated during the cell cycle. The activity of E2F transcription factors is regulated by association with specific repressor molecules that can bind and inhibit the E2F transactivation domain. For E2F-1, E2F-2, and E2F-3, the repressor is the product of the retinoblastoma gene, pRb. E2f-4 interacts with pRb-related p107 and not with pRb itself. Recently, a cDNA encoding a third member of the retinoblastoma gene family, p130, was isolated. p130 also interacts with E2F DNA binding activity, primarily in the G0 phase of the cell cycle. We report here the cloning of a fifth member of the E2F gene family. The human E2F-5 cDNA encodes a 346-amino-acid protein with a predicted molecular mass of 38 kDa. E2F-5 is more closely related to E2F-4 (78% similarity) than to E2F-1 (57% similarity). E2F-5 resembles the other E2Fs in that it binds to a consensus E2F site in a cooperative fashion with DP-1. By using a specific E2F-5 antiserum, we found that under physiological conditions, E2F-5 interacts preferentially with p130.
在许多细胞周期中表达受到严格调控的基因中都发现了E2F DNA结合位点。E2F转录因子的活性通过与特定阻遏分子结合来调节,这些阻遏分子能够结合并抑制E2F反式激活结构域。对于E2F-1、E2F-2和E2F-3而言,阻遏物是视网膜母细胞瘤基因pRb的产物。E2F-4与视网膜母细胞瘤相关的p107相互作用,而不与pRb本身相互作用。最近,编码视网膜母细胞瘤基因家族第三个成员p130的cDNA被分离出来。p130也与E2F DNA结合活性相互作用,主要在细胞周期的G0期。我们在此报告E2F基因家族第五个成员的克隆。人E2F-5 cDNA编码一种346个氨基酸的蛋白质,预测分子量为38 kDa。E2F-5与E2F-4的关系更为密切(相似度为78%),而与E2F-1的相似度为57%。E2F-5与其他E2F类似,它能与DP-1协同结合到共有E2F位点上。通过使用特异性E2F-5抗血清,我们发现在生理条件下,E2F-5优先与p130相互作用。