Regulation of Sp100A subnuclear localization and transcriptional function by EBNA-LP and interferon.
Regulation of Sp100A subnuclear localization and transcriptional function by EBNA-LP and interferon.
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DOI：
10.1089/jir.2008.0023
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发表时间：
2008-10
期刊：
影响因子：
--
通讯作者：
Chisaroka W Echendu;P. Ling
中科院分区：
文献类型：
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作者：
Chisaroka W Echendu;P. Ling
EB病毒（EBV）有效地使人B细胞永生化，并且与几种人类恶性肿瘤相关。EBV转录激活蛋白EBNA 2和EBNA 2共激活子EBNA-前导蛋白（EBNA-LP）对于B细胞永生化是重要的。我们实验室的最新观察表明，EBNA-LP共激活功能是通过与干扰素诱导基因（ISG）Sp100的相互作用介导的，导致其在早幼粒细胞白血病核小体（PML NB）中的正常位置移位到核质中。EBNA-LP和干扰素介导的机制，调节Sp100亚核定位和转录功能仍然不确定。为了澄清这些问题，我们产生了一组Sp100突变蛋白，以确定EBNA-LP是否通过干扰Sp100二聚化或通过其他结构域诱导Sp100从PML NB中置换。此外，我们测试了干扰素处理的细胞中的EBNA-LP功能。我们的研究结果表明，Sp100二聚化，PML NB定位，EBNA-LP相互作用域重叠显着。我们还表明，IFN-β不抑制EBNA-LP共激活功能。结果表明，EBNA-LP可能在EBV逃避IFN介导的抗病毒反应中发挥作用。
Epstein-Barr virus (EBV) efficiently immortalizes human B cells and is associated with several human malignancies. The EBV transcriptional activating protein EBNA2 and the EBNA2 coactivator EBNA-leader protein (EBNA-LP) are important for B cell immortalization. Recent observations from our laboratory indicate that EBNA-LP coactivation function is mediated through interactions with the interferon-inducible gene (ISG) Sp100, resulting in displacement from its normal location in promyelocytic leukemia nuclear bodies (PML NBs) into the nucleoplasm. The EBNA-LP- and interferon-mediated mechanisms that regulate Sp100 subnuclear localization and transcriptional function remain undefined. To clarify these issues, we generated a panel of Sp100 mutant proteins to ascertain whether EBNA-LP induces Sp100 displacement from PML NBs by interfering with Sp100 dimerization or through other domains. In addition, we tested EBNA-LP function in interferon-treated cells. Our results indicate that Sp100 dimerization, PML NB localization, and EBNA-LP interaction domains overlap significantly. We also show that IFN-beta does not inhibit EBNA-LP coactivation function. The results suggest that EBNA-LP might play a role in EBV-evasion of IFN-mediated antiviral responses.