Human p32: a coactivator for Epstein-Barr virus nuclear antigen-1-mediated transcriptional activation and possible role in viral latent cycle DNA replication.

Human p32: a coactivator for Epstein-Barr virus nuclear antigen-1-mediated transcriptional activation and possible role in viral latent cycle DNA replication.
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DOI:
10.1006/viro.2000.0508
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发表时间:
2000-09
期刊:
影响因子:
3.7
通讯作者:
S. Van Scoy;I. Watakabe;A. Krainer;J. Hearing
S. Van Scoy;I. Watakabe;A. Krainer;J. Hearing
中科院分区:
医学3区
文献类型:
--
作者:
S. Van Scoy;I. Watakabe;A. Krainer;J. Hearing

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eb病毒(EBV)核抗原-1 (EBNA-1)在潜伏感染的增殖细胞中维持病毒染色体是必需的,并在潜伏周期DNA复制中发挥作用。EBNA-1还可作为EBV基因表达的正调控因子和负调控因子。我们研究了EBNA-1与p32的相互作用,p32是ebv阳性伯基特淋巴瘤细胞中与EBNA-1相关的宿主线粒体蛋白。使用染色质免疫沉淀法,我们发现p32的一部分定位于DNA复制oriP的病毒潜伏周期起源。p32独立于其他蛋白质或DNA结合EBNA-1。缺乏两种p32结合元件之一的EBNA-1变体在培养细胞中与p32不稳定地相互作用,并且与oriP FR相关的报告基因的转录激活和携带oriP的质粒的复制和/或维持都存在缺陷。这些结果支持p32在EBNA-1转录激活中的作用,并表明p32在EBV潜伏周期DNA复制中起作用。
The Epstein-Barr virus (EBV) nuclear antigen-1 (EBNA-1) is required for the maintenance of the viral chromosome in latently infected, proliferating cells and plays a role in latent cycle DNA replication. EBNA-1 also functions as a positive and negative regulator of EBV gene expression. We have investigated the interaction of EBNA-1 with p32, a host mitochondrial protein that associates with EBNA-1 in EBV-positive Burkitt's lymphoma cells. Using a chromatin immunoprecipitation assay, we found that a fraction of p32 localizes to the viral latent cycle origin of DNA replication oriP in vivo. p32 binds EBNA-1 independently of other proteins or DNA. EBNA-1 variants lacking one of two p32 binding elements did not interact stably with p32 in cultured cells and were defective for both transcriptional activation of a reporter gene linked to oriP FR and replication and/or maintenance of a plasmid bearing oriP. These results support a role for p32 in transcriptional activation by EBNA-1 and suggest that p32 plays a role in EBV latent cycle DNA replication.