Document Type

Journal Article

Authors

Lijun Jiang, Department of Chemistry, Hong Kong Baptist University, Hong Kong
Rongfeng Lan, Department of Chemistry, Hong Kong Baptist University, Hong Kong
Tao Huang, Clinical Division, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong
Chi-Fai Chan, Department of Applied Biology and Chemical Technology, State Key Laboratory of Chiroscience, Hong Kong Polytechnic University, Hong Kong
Hongguang Li, Department of Chemistry, Hong Kong Baptist University, Hong Kong
Sam Lear, Department of Chemistry, Durham University, Durham, United Kingdom
Jingyi Zong, Department of Chemistry, Durham University, Durham, United Kingdom
Wing-Yan Wong, Department of Applied Biology and Chemical Technology, State Key Laboratory of Chiroscience, Hong Kong Polytechnic University, Hong Kong
Magnolia Muk-Lan Lee, Department of Applied Biology and Chemical Technology, State Key Laboratory of Chiroscience, Hong Kong Polytechnic University, Hong Kong
Brandon Dow Chan, Department of Applied Biology and Chemical Technology, State Key Laboratory of Chiroscience, Hong Kong Polytechnic University, Hong Kong
Wai-Lun Chan, Department of Chemistry, Hong Kong Baptist University, Hong Kong
Wai-Sum Lo, Department of Applied Biology and Chemical Technology, State Key Laboratory of Chiroscience, Hong Kong Polytechnic University, Hong Kong
Nai-Ki Mak, Department of Biology, Hong Kong Baptist University, Hong Kong
Maria Li Lung, Centre for Nasopharyngeal Carcinoma Research, University of Hong Kong, Hong Kong
Hong Lok Lung, Department of Biology, Hong Kong Baptist University, Hong Kong
Sai Wah Tsao, Centre for Nasopharyngeal Carcinoma Research, University of Hong Kong, Hong Kong
Graham S. Taylor, School of Cancer Sciences, University of Birmingham, Birmingham, United Kingdom
Zhao-Xiang Bian, Clinical Division, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong
William C. S. Tai, Department of Applied Biology and Chemical Technology, State Key Laboratory of Chiroscience, Hong Kong Polytechnic University, Hong Kong
Ga-Lai Law, Department of Applied Biology and Chemical Technology, State Key Laboratory of Chiroscience, Hong Kong Polytechnic University, Hong Kong
Wing-Tak Wong, Department of Applied Biology and Chemical Technology, State Key Laboratory of Chiroscience, Hong Kong Polytechnic University, Hong Kong
Steven L. Cobb, Department of Chemistry, Durham University, Durham, Hong Kong
Ka-Leung Wong, Department of Chemistry, Hong Kong Baptist University, Hong Kong

Department/Unit

Department of Biology

Language

English

Abstract

Epstein–Barr nuclear antigen 1 (EBNA1), a dimeric oncoprotein of the Epstein–Barr virus (EBV), is essential for both viral-genome maintenance and the survival of infected cells. Despite EBNA1’s potential as a therapeutic target, tools for the direct monitoring of EBNA1 in vitro and in vivo are lacking. Here, we show that a peptide-based inhibitor that luminesces when bound to EBNA1 inside the nucleus of EBV+ cells can regulate EBNA1 homodimer formation and selectively inhibit the growth of EBV+ tumours of nasopharyngeal carcinoma cells (C666-1 and NPC43) and Burkitt’s lymphoma Raji cells. We also show that the peptide-based probe leads to 93% growth inhibition of EBV+ tumours in mice. Our findings support the hypothesis that selective inhibition of EBNA1 dimerization can be used to afford better EBV-related cancer differentiation, and highlight the potential application of the probe as a new generation of biotracers for investigating the fundamental biological function of EBNA1 and for exploring its application as a therapeutic target.

Publication Date

3-2017

Source Publication Title

Nature Biomedical Engineering

Volume

1

Publisher

Nature Research

DOI

10.1038/s41551-017-0042

Link to Publisher's Edition

https://doi.org/10.1038/s41551-017-0042

ISSN (electronic)

2157846X

Included in

Biology Commons

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