Ackrill A M, Foster G R, Laxton C D, Flavell D M, Stark G R, Kerr I M
Imperial Cancer Research Fund Laboratories, London, UK.
Nucleic Acids Res. 1991 Aug 25;19(16):4387-93. doi: 10.1093/nar/19.16.4387.
Expression of the E1A oncogene of adenovirus type 5 inhibits the response of interferon (IFN)-inducible constructs to Type I (alpha,beta) and II (gamma) IFNs in transient transfection assays. In human cell lines stably expressing E1A mRNA and protein acquisition of an antiviral state and the induction of a number of genes in response to alpha- and gamma-IFNs is inhibited. A short IFN-stimulable response element (ISRE) present in the 5' flanking region of a number of genes mediates induction by alpha- and gamma-IFNs. In cells expressing E1A there is a substantial reduction in the levels of the ISRE-binding factors E and M, inducible by alpha-IFN, and of factor G, inducible by gamma-IFN. In E1A-expressing cells the E alpha subunit of factor E is activated normally in response to alpha-IFN; the defect is in the production or activation of the E gamma subunit. The inhibitory activity of E1A is lost upon deletion of the CR1 domain. The induction of HLA class II genes by gamma-IFN, which involves a different DNA response element(s), and of beta-IFN mRNA in response to double-stranded RNA are also inhibited by E1A. An essential component(s) of a number of signalling pathways must, therefore, be subject, directly or indirectly, to inhibition by E1A.
在瞬时转染实验中，5型腺病毒的E1A癌基因表达可抑制干扰素（IFN）诱导型构建体对I型（α、β）和II型（γ）干扰素的反应。在稳定表达E1A mRNA和蛋白的人细胞系中，抗病毒状态的获得以及对α和γ干扰素反应时一些基因的诱导均受到抑制。许多基因5'侧翼区域存在的一个短干扰素刺激反应元件（ISRE）介导α和γ干扰素的诱导作用。在表达E1A的细胞中，α干扰素诱导的ISRE结合因子E和M以及γ干扰素诱导的因子G的水平大幅降低。在表达E1A的细胞中，因子E的Eα亚基对α干扰素的反应正常激活；缺陷在于Eγ亚基的产生或激活。缺失CR1结构域后，E1A的抑制活性丧失。γ干扰素对HLA II类基因的诱导（涉及不同的DNA反应元件）以及双链RNA诱导β干扰素mRNA的过程也受到E1A的抑制。因此，许多信号通路的一个必需成分必定直接或间接受E1A抑制。
