Nuclear-cytoplasmic shuttling is not required for the Epstein-Barr virus EBNA-LP transcriptional coactivation function.
Nuclear-cytoplasmic shuttling is not required for the Epstein-Barr virus EBNA-LP transcriptional coactivation function.
复制标题
Epstein-Barr 病毒 EBNA-LP 转录共激活功能不需要核-胞质穿梭。
DOI：
10.1128/jvi.00654-09
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发表时间：
2009
影响因子：
5.4
通讯作者：
Peng,RongSheng
中科院分区：
文献类型：
--
作者：
Ling,PaulD;Tan,Jie;Peng,RongSheng
EB病毒（EBV）EBNA-LP是EBNA 2的转录共激活因子，其通过与早幼粒细胞白血病核小体相关蛋白Sp100 A相互作用而起作用。EBNA-LP通过蛋白质重复区域中的核定位信号的作用主要定位在细胞核中。EBNA-LP也已在细胞质中检测到，并且先前的研究表明，一些EBNA-LP共激活功能是通过将组蛋白脱乙酰酶4（HDAC 4）从细胞核重新定位到细胞质来介导的。虽然EBNA-LP可以在细胞质中发现，但它没有明显的核输出信号，并且没有直接证据表明这些细胞区室之间的主动穿梭。是否需要在细胞核和细胞质之间的主动穿梭来实现共激活仍有待澄清。为了解决这些问题，我们在种间异核体测定中测试了多种EBNA-LP同种型和突变体的核质穿梭活性以及与HDAC 4相关的能力。小于42 kDa的EBNA-LP亚型通过crm-1非依赖性机制在异核体测定中有效穿梭。此外，没有特定的EBNA-LP结构域介导的核输出可以确定。相比之下，EBNA-LP 62-kDa同种型在异核体测定中没有表现出可检测的穿梭，但仍然与较小的EBNA-LP同种型类似地共活化EBNA 2。所有测试的EBNA-LP突变体，包括共激活缺陷型Δ CR 3突变体和非穿梭62-kDa亚型，都能够与HDAC 4结合。两者合计，我们的研究结果表明，简单的扩散可能占观察到较小的EBNA-LP亚型的核出口，核质穿梭是不需要有效的EBNA-LP共激活功能，HDAC 4协会的能力是不足以介导核质穿梭或EBNA-LP共激活的情况下，与Sp100 A的功能相互作用。
Epstein-Barr virus (EBV) EBNA-LP is a transcriptional coactivator of EBNA2 that works though interaction with the promyelocytic leukemia nuclear-body-associated protein Sp100A. EBNA-LP localizes predominantly in the nucleus through the action of nuclear localization signals in the repeated regions of the protein. EBNA-LP has also been detected in the cytoplasm, and a previous study suggested that some of the EBNA-LP coactivation function is mediated by relocalizing histone deacetylase 4 (HDAC4) from the nucleus to the cytoplasm. Although EBNA-LP can be found in the cytoplasm, it has no obvious nuclear export signal, and there is no direct evidence for active shuttling between these cellular compartments. Whether active shuttling between the nucleus and cytoplasm is required for coactivation remains to be clarified. To address these issues, we tested a variety of EBNA-LP isoforms and mutants for nuclear-cytoplasmic shuttling activity in an interspecies heterokaryon assay and for the ability to associate with HDAC4. EBNA-LP isoforms smaller than 42 kDa shuttle efficiently in the heterokaryon assay via a crm-1-independent mechanism. In addition, no specific EBNA-LP domain that mediates nuclear export could be identified. In contrast, an EBNA-LP 62-kDa isoform does not demonstrate detectable shuttling in the heterokaryon assay yet still coactivates EBNA2 similarly to the smaller EBNA-LP isoforms. All of the EBNA-LP mutants tested, including the coactivation-deficient ΔCR3 mutant and the nonshuttling 62-kDa isoform, were capable of associating with HDAC4. Taken together, our results suggest that simple diffusion may account for the nuclear export observed with smaller isoforms of EBNA-LP, that nuclear-cytoplasmic shuttling is not required for efficient EBNA-LP coactivation function, and that competence for HDAC4 association is not sufficient to mediate nuclear-cytoplasmic shuttling or EBNA-LP coactivation in the absence of a functional interaction with Sp100A.