E1A-DEPENDENT TRANS-ACTIVATION OF THE HUMAN MYC PROMOTER IS MEDIATED BY THE E2F FACTOR
E1A-DEPENDENT TRANS-ACTIVATION OF THE HUMAN MYC PROMOTER IS MEDIATED BY THE E2F FACTOR
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DOI：
10.1073/pnas.86.10.3594
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发表时间：
1989-05-01
影响因子：
11.1
通讯作者：
NEVINS, JR
中科院分区：
文献类型：
--
作者：
HIEBERT, SW;LIPP, M;NEVINS, JR
E2F是一种细胞转录因子，与腺病毒E2启动子的两个位点结合。先前的实验表明E2F与E2基因的E1A依赖性转激活有关，因为在腺病毒感染期间，活性E2F的水平与E2转录的增加平行显著增加，并且E2F结合位点可以使E1A诱导异源启动子。在这里，我们发现E2F结合了人类MYC基因P2启动子中的两个序列元件，这两个序列元件位于对启动子活性至关重要的区域内。MYC启动子可以以e1a依赖的方式被反式激活，位点定向突变表明这些E2F元件对于反式激活是必不可少的。最后，我们还发现腺病毒感染静止细胞导致内源性MYC基因的刺激。我们得出结论，E2F因子的激活，可能是病毒E2转录激活的原因，也是e1a依赖性诱导MYC转录的原因。
E2F is a cellular transcription factor that binds to two sites in the adenovirus E2 promoter. Previous experiments have implicated E2F in the E1A-dependent transactivation of the E2 gene since levels of active E2F increase markedly during adenovirus infection in parallel with the increase in E2 transcription, and an E2F binding site can confer E1A inducibility to a heterologous promoter. Here we show that E2F binds two sequence elements within the P2 promoter of the human MYC gene which are within a region that is critical for promoter activity. The MYC promoter can be trans-activated in an E1A-dependent manner an site-directed mutagenesis demonstrates that these E2F elements are essential for trans-activation. Finally, we also find that adenovirus infection of quiescent cells results in a stimulation of the endogenous MYC gene. We conclude that the activation of the E2F factor, which is likely responsible for the activation of viral E2 transcription, is also responsible for the E1A-dependent induction of MYC transcription.