A ROLE FOR THE ADENOVIRUS INDUCIBLE E2F TRANSCRIPTION FACTOR IN A PROLIFERATION DEPENDENT SIGNAL TRANSDUCTION PATHWAY
A ROLE FOR THE ADENOVIRUS INDUCIBLE E2F TRANSCRIPTION FACTOR IN A PROLIFERATION DEPENDENT SIGNAL TRANSDUCTION PATHWAY
复制标题
DOI：
10.1002/j.1460-2075.1990.tb07387.x
复制
发表时间：
1990-07-01
期刊：
影响因子：
11.4
通讯作者：
NEVINS, JR
中科院分区：
文献类型：
--
作者：
MUDRYJ, M;HIEBERT, SW;NEVINS, JR
腺病毒E1 A依赖性转录的反式激活涉及利用细胞启动子特异性转录因子。一种称为E2 F的因子对于病毒E2基因的转录是重要的，并且似乎是在反式激活事件期间靶向的速率限制组分。由于E2 F是细胞来源的，可能参与细胞基因控制，我们已经确定了E2 F结合位点的细胞基因。例子包括c-myc、c-myb和N-myc原癌基因、DHFR基因和EGF受体基因。这些基因的转录受细胞增殖信号的调节，并且每个福尔斯都属于所谓的立即早期类：不依赖于新蛋白质合成而被激活的基因。由于这些共同的调节特性，我们已经解决了E2 F在生长因子依赖的转录激活中的可能作用。c-myc启动子驱动的CAT基因的表达，转染到静止的3 T3细胞中，通过添加血清刺激，而在E2 F结合位点含有突变的相同基因不响应。E2 F的DNA结合活性在血清刺激后增加4倍，并且活化动力学与c-myc转录的活化平行。此外，E2 F活性的这种增加不依赖于新的蛋白质合成，表明血清刺激导致预先存在的因子的激活。因此，这些结果提供了强有力的证据连接E2 F和增殖依赖的转录控制。我们还认为E2 F转录因子是通过刺激细胞增殖而缓慢激活的立即早期基因类调节因子的第一个例子。
Adenovirus E1A dependent trans-activation of transcription involves the utilization of cellular promoter specific transcription factors. One such factor termed E2F is important for the transcription of the viral E2 gene and appears to be a rate limiting component targeted during the trans-activation event. Since E2F is of cellular origin and likely to be involved in cellular gene control, we have identified E2F binding sites in cellular genes. Examples include the c-myc, c-myb and N-myc protoncogenes, The DHFR gene and the EGF receptor gene. The transcription of these gene is regulated by cell proliferation signals and each falls into the so-called immediate early class: genes that are activated independent of new protein synthesis. Because of these common properties of regulation, we have addressed the possible role of E2F in growth factor dependent activation of transcription. Expression of a c-myc promoter driven CAT gene, transfected into quiescent 3T3 cells, is stimulated by serum addition whereas an identical gene containing mutations in the E2F binding sites is not responsive. The DNA binding activity of E2F is increased 4-fold upon serum stimulation and the kinetics of activation parallel activation of c-myc transcription. Furthermore, this increase in E2F activity is independent of new protein synthesis indicating that serum stimulation results in an activation of a pre-existing factor. These results thus provide strong evidence linking E2F and proliferation dependent control of transcription. We also believe that the E2F transcription factor is the first example of a regulator of the class of immediate early genes that is slowly activated by stimulated of cell proliferation.