Böhnlein E, Lowenthal J W, Siekevitz M, Ballard D W, Franza B R, Greene W C
Howard Hughes Medical Institute, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
Cell. 1988 Jun 3;53(5):827-36. doi: 10.1016/0092-8674(88)90099-2.
Both the interleukin-2 receptor-alpha (Tac, p55, IL-2R alpha) gene and the long terminal repeat (LTR) of type 1 HIV are activated by various T cell mitogens. We now demonstrate that an inducible 86 kd nuclear protein termed HIVEN86A specifically binds to both the enhancer element of the HIV-1 LTR and a closely related 12 bp sequence present in the 5' regulatory region (-267 to -256) of the IL-2R alpha gene. The interaction of these binding sites with HIVEN86A and perhaps other cellular proteins such as NF-kappa B appears importantly involved in mitogen activation since the isolated IL-2R alpha promoter binding site or single elements of the normally duplicated HIV-1 enhancer alone are sufficient to confer mitogen inducibility on an unresponsive heterologous promoter. Together these findings suggest that the normal action of an inducible nuclear DNA binding protein(s) involved in the regulation of IL-2R alpha gene expression can be subverted by the HIV-1 provirus to promote activation of retroviral gene transcription.
白细胞介素-2受体α（Tac、p55、IL-2Rα）基因和1型HIV的长末端重复序列（LTR）均可被多种T细胞有丝分裂原激活。我们现在证明，一种名为HIVEN86A的可诱导86kd核蛋白可特异性结合HIV-1 LTR的增强子元件以及IL-2Rα基因5'调控区（-267至-256）中存在的一个密切相关的12bp序列。这些结合位点与HIVEN86A以及可能的其他细胞蛋白（如NF-κB）的相互作用似乎在有丝分裂原激活中起重要作用，因为单独分离的IL-2Rα启动子结合位点或正常重复的HIV-1增强子的单个元件就足以赋予无反应的异源启动子有丝分裂原诱导性。这些发现共同表明，参与IL-2Rα基因表达调控的可诱导核DNA结合蛋白的正常作用可被HIV-1前病毒颠覆，以促进逆转录病毒基因转录的激活。
