Bergman Y, Shavit D
Hubert H. Humphrey Center for Experimental Medicine and Cancer Research, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
J Immunol. 1988 Mar 15;140(6):2073-80.
Proteins encoded by early region 1A (E1A) regulate transcription of viral and cellular genes. The mechanism of this trans-activation is not understood, but is of considerable interest as an example of transcription regulation through a cellular intermediate. We have therefore studied the effect of E1A products on the activity of the kappa L chain gene promoter and enhancer. By using transient and stable transfections into lymphoid and nonlymphoid cells, we found that the E1A proteins have a pleiotropic effect on the regulation of the mouse kappa-chain gene enhancer. In lymphoid cells the E1A products repress kappa-chain enhancer, whereas in fibroblasts, the kappa-chain enhancer is activated by the E1A products whether the E1A gene is in an extrachromosomal location or stably integrated in the genome. Furthermore, a functional kappa-chain promoter, containing the octanucleotide and "TATA" sequences is needed in order to be transcribed in E1A-producing cells. This ability of E1A products to negatively and positively regulate kappa-chain transcription may reflect a more general phenomenon in which a given cellular protein could participate in a variety of different cellular controls.
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。这种反式激活的机制尚不清楚,但作为通过细胞中间体进行转录调控的一个例子,它具有相当大的研究价值。因此,我们研究了E1A产物对κ轻链基因启动子和增强子活性的影响。通过对淋巴细胞和非淋巴细胞进行瞬时和稳定转染,我们发现E1A蛋白对小鼠κ链基因增强子的调控具有多效性。在淋巴细胞中,E1A产物会抑制κ链增强子,而在成纤维细胞中,无论E1A基因是位于染色体外还是稳定整合在基因组中,κ链增强子都会被E1A产物激活。此外,为了在产生E1A的细胞中进行转录,需要一个包含八聚体和“TATA”序列的功能性κ链启动子。E1A产物对κ链转录进行正负调控的这种能力,可能反映了一种更普遍的现象,即特定的细胞蛋白可能参与多种不同的细胞调控。