A peptide inhibitor of exportin1 blocks shuttling of the adenoviral E1B 55 kDa protein but not export of viral late mRNAs

A peptide inhibitor of exportin1 blocks shuttling of the adenoviral E1B 55 kDa protein but not export of viral late mRNAs
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DOI:
10.1016/j.virol.2005.04.007
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发表时间:
2005-06-20
期刊:
影响因子:
3.7
通讯作者:
Kyin, S
Kyin, S
中科院分区:
医学3区
文献类型:
--
作者:
Flint, SJ;Huang, WY;Kyin, S

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人C亚群腺病毒E1B55 kDa和E4 Orf6蛋白是病毒晚期mRNA有效核输出所必需的,但介导这种输出的细胞途径尚未确定。作为开发解决这个问题的一般方法的第一步,我们评估了细胞输出受体的细胞渗透性肽抑制剂的效用。由于E1 B和E4蛋白都含有富含亮氨酸的核输出信号(内斯),我们合成了含有这种内斯的细胞渗透性肽。该肽诱导E1B蛋白输出的实质性抑制,而对照、非功能性肽没有。然而,在相同条件下,内斯肽对病毒晚期mRNA的输出没有影响。这些观察结果证实了病毒晚期mRNA不通过exportin1输出,以及肽抑制剂在腺病毒感染细胞中mRNA输出调节研究中的价值。(c)2005年爱思唯尔公司All rights reserved.
The human subgroup C adenoviral E1B55 kDa and E4 Orf6 proteins are required for efficient nuclear export of viral late mRNAs, but the cellular pathway that mediates such export has not been identified. As a first step to develop a general approach to address this issue, we have assessed the utility of cell-permeable peptide inhibitors of cellular export receptors. As both E1B and E4 proteins have been reported to containing a leucine-rich nuclear export signal (NES), we synthesized a cell-permeable peptide containing such an NES. This peptide induced substantial inhibition of export of the E1B protein, whereas a control, non-functional peptide did not. However, under the same conditions, the NES peptide had no effect on export of viral late mRNAs. These observations establish that viral late mRNAs are not exported by exportin1, as well as the value of peptide inhibitors in investigation of mRNA export regulation in adenovirus-infected cells. (c) 2005 Elsevier Inc. All rights reserved.