An adenovirus E4 gene product trans-activates E2 transcription and stimulates stable E2F binding through a direct association with E2F.
An adenovirus E4 gene product trans-activates E2 transcription and stimulates stable E2F binding through a direct association with E2F.
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腺病毒 E4 基因产物反式激活 E2 转录并通过与 E2F 直接关联刺激稳定的 E2F 结合。
DOI：
10.1073/pnas.87.5.2008
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发表时间：
1990
影响因子：
11.1
通讯作者：
Nevins,JR
中科院分区：
文献类型：
--
作者：
Neill,SD;Hemstrom,C;Virtanen,A;Nevins,JR
腺病毒E4基因编码可刺激E2启动子的反式激活功能。E4反式激活所需的E2启动子序列与E1 A反式激活所需的序列相同，这些序列主要是E2启动子结合因子（E2 F）结合位点。此外，E2 F DNA结合活性的完全激活需要E1 A和E4两者的作用。一系列突变E4病毒的分析鉴定E4转录单位的开放阅读框（orf）6/7为激活E2 F结合活性所需的。此外，各种E4 cDNA的分析表明，E4 orf 6/7也负责E2转录的反式激活。在网织红细胞提取物中，E4 orf 6/7 mRNA的翻译，而不是对照mRNA的翻译，产生了可以刺激E2 F在体外协同结合的活性，这与最近的体内试验一致，该试验证明了E4基因在E2 F稳定复合物形成中的作用。这种刺激是由于E4蛋白与E2 F的直接相互作用，因为识别E4 orf 6/7多肽的抗体检测E2 F-DNA复合物中的E4蛋白。我们得出结论，E4 ORF 6/7产品与E2 F因子相互作用，改变结合，以允许形成一个稳定的复合物，导致刺激转录。
The adenovirus E4 gene encodes a trans-activating function that can stimulate the E2 promoter. E2 promoter sequences required for E4 trans-activation are identical to those required for E1A trans-activation, and these principally are the E2 promoter binding factor (E2F) binding sites. Furthermore, full activation of E2F DNA binding activity requires both E1A and E4 action. Analysis of a series of mutant E4 viruses identifies open reading frame (orf) 6/7 of the E4 transcription unit as that required for activation of E2F binding activity. In addition, the assay of various E4 cDNAs demonstrates that the E4 orf 6/7 also is responsible for the trans-activation of E2 transcription. Translation of the E4 orf 6/7 mRNA, but not a control mRNA, in a reticulocyte extract generates an activity that can stimulate cooperative binding of E2F in vitro, consistent with recent in vivo assays that demonstrate a role for the E4 gene in E2F stable complex formation. This stimulation is due to a direct interaction of the E4 protein with E2F since an antibody that recognizes the E4 orf 6/7 polypeptide detects this E4 protein in the E2F-DNA complex. We conclude that the E4 orf 6/7 product interacts with the E2F factor altering binding to allow formation of a stable complex that results in a stimulation of transcription.