B1.12: a novel peptide interacting with the extracellular loop of the EBV oncoprotein LMP1

被引:7
作者
Ammous-Boukhris, Nihel [1 ]
Mosbah, Amor [2 ]
Ayadi, Wajdi [1 ]
Sahli, Emna [5 ]
Chevance, Soizic [3 ]
Bondon, Arnaud [3 ,4 ]
Gargouri, Ali [1 ]
Baudy-Floc'h, Michele [3 ]
Mokdad-Gargouri, Raja [1 ]
机构
[1] Univ Sfax, Ctr Biotechnol Sfax, Lab Mol Biotechnol Eukaryotes, Sfax, Tunisia
[2] Univ Manouba, Biotechnopole Sidi Thabet, ISBST, BVBGR LR 11ES31, Ariana 2020, Tunisia
[3] Univ Rennes 1, COrInt, ISCR UMR CNRS 6226, Rennes, France
[4] Univ Rennes 1, Plate Forme PRISM, SFR UMS CNRS 3480, INSERM 018,Biosit, Rennes, France
[5] Univ Sfax, Ctr Biotechnol Sfax, Plate Forme Anal, Sfax, Tunisia
关键词
NASOPHARYNGEAL CARCINOMA-CELLS; EPSTEIN-BARR-VIRUS; PHAGE-DISPLAY; PROTEIN EXPRESSION; BINDING; CANCER; IDENTIFICATION; TRANSPORTER; REFINEMENT; GROWTH;
D O I
10.1038/s41598-019-39732-y
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Latent membrane protein 1 (LMP1) encoded by the Epstein-Barr virus (EBV) plays an important role in EBV-induced cell transformation. Down-regulation of the LMP1 expression had shown promising results on cancer cell therapy. In this study, we identified by Phage display a novel peptide called B1.12 (ACPLDLRSPCG) which selectively binds to the extracellular loop (B1) of the LMP1 oncoprotein as demonstrated by molecular docking, NMR and ITC. Using an LMP1 expressing cell line, we showed that B1.12 decreased cell viability, and induced G0/G1 cell cycle arrest. In addition, the expression of A20, pAkt, and pNFkb (pRelA536) in C666-1 cells treated with B1.12 decreased compared to the untreated cells. In conclusion, we selected a novel peptide able to bind specifically to the extracellular loop of LMP1 and thus modulate its oncogenic properties.
引用
收藏
页数:12
相关论文
共 38 条
[11]   Structure of the YajR transporter suggests a transport mechanism based on the conserved motif A [J].
Jiang, Daohua ;
Zhao, Yan ;
Wang, Xianping ;
Fan, Junping ;
Heng, Jie ;
Liu, Xuehui ;
Feng, Wei ;
Kang, Xusheng ;
Huang, Bo ;
Liu, Jianfeng ;
Zhang, Xuejun Cai .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2013, 110 (36) :14664-14669
[12]   The Latent Membrane Protein 1 (LMP1) [J].
Kieser, Arnd ;
Sterz, Kai R. .
EPSTEIN BARR VIRUS, VOL 2: ONE HERPES VIRUS: MANY DISEASES, 2015, 391 :119-149
[13]   The use of phage-displayed peptide libraries to develop tumor-targeting drugs [J].
Krumpe, LRH ;
Mori, T .
INTERNATIONAL JOURNAL OF PEPTIDE RESEARCH AND THERAPEUTICS, 2006, 12 (01) :79-91
[14]  
LAHERTY CD, 1992, J BIOL CHEM, V267, P24157
[15]   Modulation of LMP1 protein expression by EBV-encoded microRNAs [J].
Lo, Angela Kwok Fung ;
To, Ka Fai ;
Lo, Kwok Wai ;
Lung, Raymond Wai Ming ;
Hui, Jan Wai Ying ;
Liao, Gangling ;
Hayward, S. Diane .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (41) :16164-16169
[16]   Effect of EBV LMP1 targeted DNAzymes on cell proliferation and apoptosis [J].
Lu, ZX ;
Ye, M ;
Yan, GR ;
Li, Q ;
Tang, M ;
Lee, LM ;
Sun, LQ ;
Cao, Y .
CANCER GENE THERAPY, 2005, 12 (07) :647-654
[17]   Screening of a specific peptide binding to esophageal squamous carcinoma cells from phage displayed peptide library [J].
Ma, Caixia ;
Li, Chunyan ;
Jiang, Dongliang ;
Gao, Xiaojie ;
Han, Juanjuan ;
Xu, Nan ;
Wu, Qiong ;
Nie, Guochao ;
Chen, Wei ;
Lin, Fenghuei ;
Hou, Yingchun .
MOLECULAR AND CELLULAR PROBES, 2015, 29 (03) :182-189
[18]   Unique signaling properties of CTAR1 in LMP1-Mediated transformation [J].
Mainou, Bernardo A. ;
Everly, David N., Jr. ;
Raab-Traub, Nancy .
JOURNAL OF VIROLOGY, 2007, 81 (18) :9680-9692
[19]   An integrated suite of fast docking algorithms [J].
Mashiach, Efrat ;
Schneidman-Duhovny, Dina ;
Peri, Aviyah ;
Shavit, Yoli ;
Nussinov, Ruth ;
Wolfson, Haim J. .
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS, 2010, 78 (15) :3197-3204
[20]   Silencing of LMP1 induces cell cycle arrest and enhances chemosensitivity through inhibition of AKT signaling pathway in EBV-positive nasopharyngeal carcinoma cells [J].
Mei, Yu-Ping ;
Zhou, Jun-Min ;
Wang, Yi ;
Huang, He ;
Deng, Rong ;
Feng, Gong-Kan ;
Zeng, Yi-Xin ;
Zhu, Xiao-Feng .
CELL CYCLE, 2007, 6 (11) :1379-1385