Strobl L J, Höfelmayr H, Marschall G, Brielmeier M, Bornkamm G W, Zimber-Strobl U
GSF-National Research Center for Environment and Health, Institute for Clinical Molecular Biology and Tumor Genetics, D-81377 Munich, Germany.
J Virol. 2000 Feb;74(4):1727-35. doi: 10.1128/jvi.74.4.1727-1735.2000.
Both Epstein-Barr viral nuclear antigen 2 (EBNA2) and activated Notch transactivate genes by interacting with the transcription factor RBP-Jkappa. The viral protein EBNA2 may hence be regarded as a functional equivalent of an activated Notch receptor. Until now, nothing has been known about the physiological role of Notch signaling in B cells. Here we investigated whether activated Notch can induce the same phenotypic changes as EBNA2 in Burkitt's lymphoma cells. An estrogen receptor fusion protein of the intracellular part of mouse Notch 1 (mNotch1-IC), mimicking in the presence of estrogen a constitutively active Notch receptor, was stably transfected into the Burkitt's lymphoma cell lines BL41-P3HR1 and HH514. Northern blot analysis revealed that the LMP2A gene is induced by Notch-IC in the presence of estrogen, whereas increased expression of LMP1 could be detected only if cycloheximide was simultaneously added. Concerning the cellular genes regulated by EBNA2, Notch-IC was able to upregulate CD21 but not CD23 expression. Immunoglobulin mu (Igmu) expression, which is downregulated by EBNA2, was also negatively regulated by Notch-IC. Similarly to EBNA2, Notch-IC was able to repress c-myc expression, which is under the control of the immunoglobulin heavy-chain locus in Burkitt's lymphoma cells with a t(8;14) translocation. The data show that Notch-IC is able to participate in gene regulation in B cells.
爱泼斯坦-巴尔病毒核抗原2（EBNA2）和活化的Notch均通过与转录因子RBP-Jκ相互作用来反式激活基因。因此，病毒蛋白EBNA2可被视为活化的Notch受体的功能等效物。到目前为止，尚不清楚Notch信号在B细胞中的生理作用。在此，我们研究了活化的Notch是否能在伯基特淋巴瘤细胞中诱导与EBNA2相同的表型变化。将小鼠Notch 1细胞内部分（mNotch1-IC）的雌激素受体融合蛋白在雌激素存在下模拟组成型活化的Notch受体，稳定转染至伯基特淋巴瘤细胞系BL41-P3HR1和HH514中。Northern印迹分析显示，在雌激素存在下，LMP2A基因由Notch-IC诱导，而只有同时添加环己酰亚胺时才能检测到LMP1表达增加。关于受EBNA2调节的细胞基因，Notch-IC能够上调CD21的表达，但不能上调CD23的表达。EBNA2下调的免疫球蛋白μ（Igμ）表达也受到Notch-IC的负调节。与EBNA2类似，Notch-IC能够抑制c-myc的表达，在具有t(8;14)易位的伯基特淋巴瘤细胞中，c-myc受免疫球蛋白重链基因座的控制。数据表明，Notch-IC能够参与B细胞中的基因调控。
