Kuppuswamy M N, Chinnadurai G
Virology. 1987 Jul;159(1):31-8. doi: 10.1016/0042-6822(87)90344-8.
The E1a region of adenoviruses encodes two early proteins of 289 amino acids (289R) and 243R from two differentially spliced mRNAs of 13 and 12 S, respectively. These E1a proteins of adenoviruses are multifunctional and have been shown to play an essential role in cellular immortalization and transformation. The E1a gene is also known to regulate the expression of certain viral and cellular genes in a positive or negative manner. To identify the domains of the E1a proteins required for their transformation and transcriptional regulatory functions, we have constructed and analyzed several E1a mutations. A region located between amino acid residues 125 and 127 appears to be essential for cell transformation in cooperation with both E1b and the activated cellular oncogene, T24 Har-ras. Mutation at this region does not affect the ability of E1a to trans-activate the Ad2 early E2 promoter significantly. Our experiments have not revealed the domain of E1a most essential for trans-repression. However, the region between amino acid residues 125 and 127 appears to have a small effect on E1a-mediated repression of the immunoglobulin heavy-chain and polyoma enhancers but has no significant effect on the SV40 enhancer. From our results, it appears that the transformation function of E1a can be dissociated from its transcriptional regulatory functions.
腺病毒的E1a区域分别从13S和12S的两种差异剪接mRNA中编码两种早期蛋白，即289个氨基酸的289R蛋白和243R蛋白。腺病毒的这些E1a蛋白具有多种功能，已被证明在细胞永生化和转化中起重要作用。E1a基因还以正向或负向方式调节某些病毒和细胞基因的表达。为了确定E1a蛋白的转化和转录调节功能所需的结构域，我们构建并分析了几种E1a突变体。位于氨基酸残基125和127之间的区域似乎对于与E1b和激活的细胞癌基因T24 Har-ras协同进行细胞转化至关重要。该区域的突变不会显著影响E1a反式激活Ad2早期E2启动子的能力。我们的实验尚未揭示E1a反式抑制最关键的结构域。然而，氨基酸残基125和127之间的区域似乎对E1a介导的免疫球蛋白重链和多瘤病毒增强子的抑制有较小影响，但对SV40增强子没有显著影响。从我们的结果来看，E1a的转化功能似乎可以与其转录调节功能分离。
