Repression of the interferon signal transduction pathway by the adenovirus E1A oncogene.
Repression of the interferon signal transduction pathway by the adenovirus E1A oncogene.
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腺病毒 E1A 癌基因抑制干扰素信号转导途径。
DOI：
10.1073/pnas.88.18.7913
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发表时间：
1991
影响因子：
11.1
通讯作者：
Reich,NC
中科院分区：
文献类型：
--
作者：
Gutch,MJ;Reich,NC
由I型干扰素（α和β干扰素）启动的信号转导途径受到5型腺病毒E1A癌基因表达的抑制。与E1A癌基因和干扰素刺激的报告基因的共转染分析表明，E1A癌蛋白的氨基末端结构域内的突变是有缺陷的转录抑制。共转染实验还表明，转录抑制介导的干扰素刺激的基因的启动子内发现的干扰素刺激的反应元件（ISRE）。由于干扰素治疗激活了一个潜在的细胞质DNA结合因子，可以识别ISRE，随后刺激转录，该因子的外观进行了分析，在组成型表达E1A癌基因的细胞系。发现这种转录激活因子的DNA结合活性在E1A表达细胞系中被抑制。在体外细胞质混合实验中，从控制和E1A表达细胞提取物确定了一个特定的组成部分，这种多聚体转录因子是有缺陷的。
The signal transduction pathway initiated by type I interferon (alpha and beta interferons) is inhibited by expression of the adenovirus type 5 E1A oncogene. Cotransfection analyses with the E1A oncogene and an interferon-stimulated reporter gene show that mutations within an amino-terminal domain of the E1A oncoprotein are defective in transcriptional repression. Cotransfection experiments also revealed that the transcriptional repression is mediated through the interferon-stimulated response element (ISRE) found within the promoter of interferon-stimulated genes. Since interferon treatment activates a latent cytoplasmic DNA-binding factor that can recognize the ISRE and subsequently stimulate transcription, the appearance of this factor was analyzed in a cell line that constitutively expresses the E1A oncogene. The DNA binding activity of this transcriptional activator was found to be inhibited in the E1A-expressing cell line. In vitro cytoplasmic mixing experiments with extracts from control and E1A-expressing cells identified a specific component of this multimeric transcription factor to be defective.