Strobl L J, Höfelmayr H, Stein C, Marschall G, Brielmeier M, Laux G, Bornkamm G W, Zimber-Strobl U
GSF-Forschungszentrum für Umwelt und Gesundheit, Institut für Klinische Molekularbiologie und Tumorgenetik, München, Germany.
Immunobiology. 1997 Dec;198(1-3):299-306. doi: 10.1016/s0171-2985(97)80050-2.
The Epstein-Barr viral nuclear antigen 2 (EBNA2) plays a key role during establishment and maintenance of B cell immortalization after Epstein-Barr virus (EBV) infection. EBNA2 acts as a transactivator of cellular and viral genes. We studied two EBNA2 regulated viral promoters (TP1 promoter and LMP/TP2 promoter) in detail to learn more about the molecular mechanisms of EBNA2-mediated transactivation. In both promoters we could identify at least one binding site for the cellular repressor protein RBP-J kappa. EBNA2 is tethered to the EBNA2 responsive promoter elements by interaction with this cellular protein. Although necessary, the binding of RBP-J kappa is not sufficient for EBNA2-mediated transactivation. At least two further cellular proteins, which are different in the studied promoters are important for efficient transactivation. The identification of RBP-J kappa as central mediator of EBNA2 transactivation suggested an interference of EBNA2 with the highly conserved Notch receptor signal transduction pathway. We could show that an activated form of the Notch receptor can transactivate a reporter construct containing a hexamer of the two RBP-J kappa binding sites of the TP1 promoter supporting the idea that EBNA2 acts as a functional equivalent of an activated Notch receptor.
爱泼斯坦-巴尔病毒核抗原2（EBNA2）在爱泼斯坦-巴尔病毒（EBV）感染后B细胞永生化的建立和维持过程中起关键作用。EBNA2作为细胞和病毒基因的反式激活因子。我们详细研究了两个受EBNA2调控的病毒启动子（TP1启动子和LMP/TP2启动子），以更多地了解EBNA2介导的反式激活的分子机制。在这两个启动子中，我们都能鉴定出至少一个细胞阻遏蛋白RBP-Jκ的结合位点。EBNA2通过与这种细胞蛋白相互作用而与EBNA2反应性启动子元件相连。虽然RBP-Jκ的结合是必要的，但它不足以实现EBNA2介导的反式激活。在研究的启动子中至少还有另外两种不同的细胞蛋白对有效的反式激活很重要。RBP-Jκ被鉴定为EBNA2反式激活的中心介质，这表明EBNA2干扰了高度保守的Notch受体信号转导途径。我们可以证明，Notch受体的激活形式可以反式激活一个报告构建体，该构建体包含TP1启动子的两个RBP-Jκ结合位点的六聚体，这支持了EBNA2作为激活的Notch受体功能等效物的观点。
