van Dam H, Offringa R, Smits A M, Bos J L, Jones N C, van der Eb A J
Laboratory for Molecular Carcinogenesis, University of Leiden, The Netherlands.
Oncogene. 1989 Oct;4(10):1207-12.
The growth factor-inducible cellular genes JE, c-myc and stromelysin (sml) are strongly repressed upon transformation by adenovirus E1A. As E1A proteins are multifunctional and apparently contain distinct domains (conserved regions 1, 2 and 3), each with a specific effect on gene regulation and cell-transformation, we have investigated which of the three conserved regions are responsible for the reduced expression of these genes. To this end, we monitored the expression of the JE, sml and c-myc genes in a panel of normal rat kidney (NRK) cells expressing different mutant E1A genes. Only CR1, and not CR2 or CR3 were found to be essential for the repression of the genes, indicating that CR1, one of the regions essential for cell transformation, represents an autonomous gene regulatory function that can operate in the absence of CR2. We also show that the association of E1A proteins to a 300 kD cellular protein in NRK cells coincides with the ability to repress these genes.
生长因子诱导的细胞基因JE、c-myc和基质溶解素（sml）在被腺病毒E1A转化后受到强烈抑制。由于E1A蛋白具有多种功能，且明显包含不同的结构域（保守区域1、2和3），每个结构域对基因调控和细胞转化都有特定作用，我们研究了这三个保守区域中哪一个负责这些基因表达的降低。为此，我们监测了一组表达不同突变E1A基因的正常大鼠肾（NRK）细胞中JE、sml和c-myc基因的表达。结果发现，只有保守区域1（CR1）对这些基因的抑制是必需的，而保守区域2（CR2）和保守区域3（CR3）并非必需，这表明CR1作为细胞转化所必需的区域之一，代表了一种独立的基因调控功能，其在没有CR2的情况下也能发挥作用。我们还表明，E1A蛋白与NRK细胞中一种300 kD细胞蛋白的结合与抑制这些基因的能力相一致。
