Engel D A, Muller U, Gedrich R W, Eubanks J S, Shenk T
Howard Hughes Medical Institute, Department of Molecular Biology, Princeton University, NJ 08544.
Proc Natl Acad Sci U S A. 1991 May 1;88(9):3957-61. doi: 10.1073/pnas.88.9.3957.
Products of the adenovirus E1A gene can act synergistically with cAMP to activate transcription of several viral early genes and the cellular genes c-fos and jun-B. Transcription factor AP-1-binding activity is also induced by the combined action of E1A and cAMP. Mouse S49 cells were infected with adenovirus variants expressing either the 243- or 289-amino acid E1A protein and treated with the cAMP analog dibutyryl-cAMP. Significant E1A-dependent induction of c-fos mRNA and AP-1-binding activity was observed in cells expressing either E1A protein. These effects absolutely required the presence of cAMP. In contrast, the 243-amino acid protein was a poor activator of the viral early genes E2 and E4 compared with the 289-amino acid protein. These data suggest that the 243- and 289-amino acid E1A proteins both interact functionally with the cAMP signaling system to activate transcription of a cellular gene and AP-1-binding activity. The mechanism involved in this process is probably different from the mechanism of transcriptional activation of viral genes.
腺病毒E1A基因的产物可与cAMP协同作用，激活多个病毒早期基因以及细胞基因c-fos和jun-B的转录。转录因子AP-1结合活性也可由E1A和cAMP的联合作用诱导产生。用表达243个氨基酸或289个氨基酸的E1A蛋白的腺病毒变体感染小鼠S49细胞，并用cAMP类似物二丁酰-cAMP处理。在表达任一E1A蛋白的细胞中均观察到显著的E1A依赖性c-fos mRNA诱导和AP-1结合活性。这些效应绝对需要cAMP的存在。相比之下，与289个氨基酸的蛋白相比，243个氨基酸的蛋白对病毒早期基因E2和E4的激活作用较差。这些数据表明，243个氨基酸和289个氨基酸的E1A蛋白在功能上均与cAMP信号系统相互作用，以激活细胞基因的转录和AP-1结合活性。该过程涉及的机制可能与病毒基因转录激活的机制不同。
