2011年12月
DNA ligand designed to antagonize EBNA1 represses Epstein-Barr virus-induced immortalization
CANCER SCIENCE
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- 巻
- 102
- 号
- 12
- 開始ページ
- 2221
- 終了ページ
- 2230
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1111/j.1349-7006.2011.02098.x
- 出版者・発行元
- WILEY-BLACKWELL
EpsteinBarr virus (EBV) transforms human B lymphocytes into immortalized cells in vitro and is associated with various malignancies in vivo. EBNA1, which is expressed in the majority of EBV-infected cells, recognizes specific DNA sequences at the cis-acting latent origin of plasmid replication (oriP) element of the EBV genome. EBNA1 plays a critical role in the viral episome maintenance and transactivates viral transforming genes in latently infected cells. Therefore, DNA-targeting agents that can disrupt the EBNA1oriP interaction will offer novel functional inhibitors of EBNA1. Pyrroleimidazole polyamides, sequence-specific DNA ligands, can be designed to interfere with the binding of various transcriptional factors. Here, we synthesized pyrroleimidazole polyamides targeting EBNA1-bound DNA sequences and developed an inhibitor for the EBNA1oriP interaction. A pyrrole-imidazole polyamide, designated as DSE-3, bound adjacent to the EBNA1 recognition sequences located in the dyad symmetry element of oriP, and selectively inhibited EBNA1oriP binding both in vitro and in vivo. DSE-3 also inhibited the proliferation of established lymphoblastoid cell lines by eradicating EBV episomes from the cells. In addition, DSE-3 repressed the expression of viral transforming genes after infecting human peripheral blood mononuclear cells with EBV and, as a consequence, inhibited EBV-mediated B-cell immortalization. These results suggest that EBNA1 functions will be an attractive pharmacological target for EBV-associated diseases. (Cancer Sci 2011; 102: 22212230)
- リンク情報
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- DOI
- https://doi.org/10.1111/j.1349-7006.2011.02098.x
- J-GLOBAL
- https://jglobal.jst.go.jp/detail?JGLOBAL_ID=201102286105863846
- CiNii Articles
- http://ci.nii.ac.jp/naid/10030246127
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/21910783
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000297202800015&DestApp=WOS_CPL
- ID情報
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- DOI : 10.1111/j.1349-7006.2011.02098.x
- ISSN : 1347-9032
- J-Global ID : 201102286105863846
- CiNii Articles ID : 10030246127
- PubMed ID : 21910783
- Web of Science ID : WOS:000297202800015