Shurman L, Sen R, Bergman Y
Hubert H. Humphrey Center for Experimental Medicine and Cancer Research, Hebrew University, Jerusalem, Israel.
J Immunol. 1989 Dec 1;143(11):3806-12.
Proteins encoded by the early region 1A (E1A) regulate transcription of viral and cellular genes. The mechanism of this trans-regulation remains unclear but it is of considerable interest as an example of transcription regulation through cellular intermediates. We have therefore studied the effect of E1A products on the activity of the k-L chain gene enhancer. In our previous studies we have found that the k-chain enhancer is activated by E1A products in fibroblasts. Using in vivo competition experiments we found that the E1A regulatory effect involves trans-acting factors that can be titrated out by the k-chain enhancer sequences. Our transfection experiments suggest that the k3 enhancer fragment, encompassing the NF-kB binding site, is one of the sites through which the adenovirus E1A products exert their transactivation effect. The level of the nuclear factors that bind to the NF-kB binding site increases in fibroblasts that constitutively express E1A products. Understanding the mechanisms through which E1A regulates transcription should help to illuminate cellular mechanisms of gene control in normal and transformed cells.
早期区域1A(E1A)编码的蛋白质可调节病毒和细胞基因的转录。这种反式调节的机制尚不清楚,但作为通过细胞中间体进行转录调节的一个例子,它具有相当大的研究价值。因此,我们研究了E1A产物对κ轻链基因增强子活性的影响。在我们之前的研究中,我们发现κ链增强子在成纤维细胞中被E1A产物激活。通过体内竞争实验,我们发现E1A的调节作用涉及可被κ链增强子序列滴定掉的反式作用因子。我们的转染实验表明,包含NF-κB结合位点的κ3增强子片段是腺病毒E1A产物发挥反式激活作用的位点之一。在组成型表达E1A产物的成纤维细胞中,与NF-κB结合位点结合的核因子水平会升高。了解E1A调节转录的机制应有助于阐明正常细胞和转化细胞中基因控制的细胞机制。