爱泼斯坦-巴尔病毒核抗原2对Notch1受体细胞内区域的功能替代
Functional replacement of the intracellular region of the Notch1 receptor by Epstein-Barr virus nuclear antigen 2.
作者信息
Sakai T, Taniguchi Y, Tamura K, Minoguchi S, Fukuhara T, Strobl L J, Zimber-Strobl U, Bornkamm G W, Honjo T
机构信息
Department of Medical Chemistry, Kyoto University Faculty of Medicine, Yoshida, Sakyo-ku, Kyoto 606, Japan.
出版信息
J Virol. 1998 Jul;72(7):6034-9. doi: 10.1128/JVI.72.7.6034-6039.1998.
Abstract
The intracellular region (RAMIC) of the mouse Notch1 receptor interacts with RBP-J/CBF-1, which binds to the DNA sequence CGTGGGAA and suppresses differentiation by transcriptional activation of genes regulated by RBP-J. Epstein-Barr virus nuclear antigen 2 (EBNA2) is essential for immortalization of human B cells by the virus. EBNA2 is a pleiotropic activator of viral and cellular genes and is targeted to DNA at least in part by interacting with RBP-J. We found that EBNA2 and the Notch1 RAMIC compete for binding to RBP-J, indicating that their interaction sites on RBP-J overlap at least partially. EBNA2 and Notch1 RAMIC transactivated the same set of viral and host promoters, i.e., the EBNA2 response element of the Epstein-Barr virus TP1 and the HES-1 promoter. Furthermore, EBNA2 functionally replaced the Notch1 RAMIC by suppressing differentiation of C2C12 myoblast progenitor cells.
摘要
小鼠Notch1受体的细胞内区域（RAMIC）与RBP-J/CBF-1相互作用，RBP-J/CBF-1与DNA序列CGTGGGAA结合，并通过转录激活受RBP-J调控的基因来抑制分化。爱泼斯坦-巴尔病毒核抗原2（EBNA2）对于该病毒使人类B细胞永生化至关重要。EBNA2是病毒和细胞基因的多效性激活剂，并且至少部分地通过与RBP-J相互作用而靶向DNA。我们发现EBNA2和Notch1 RAMIC竞争与RBP-J的结合，这表明它们在RBP-J上的相互作用位点至少部分重叠。EBNA2和Notch1 RAMIC激活了同一组病毒和宿主启动子，即爱泼斯坦-巴尔病毒TP1的EBNA2反应元件和HES-1启动子。此外，EBNA2通过抑制C2C12成肌细胞祖细胞的分化在功能上取代了Notch1 RAMIC。
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