@Article{096504021X16135618512563,
AUTHOR = {Hongde Li, Yueshuo Li, Jianmin Hu, Sufang Liu, Xiangjian Luo, Min Tang, 
Ann M. Bode, Zigang Dong, Xinqi Liu, Weihua Liao, Ya Cao},
TITLE = {(−)-Epigallocatechin-3-Gallate Inhibits EBV Lytic Replication via Targeting  LMP1-Mediated MAPK Signal Axes},
JOURNAL = {Oncology Research},
VOLUME = {28},
YEAR = {2020},
NUMBER = {7-8},
PAGES = {763--778},
URL = {http://www.techscience.com/or/v28n7-8/48466},
ISSN = {1555-3906},
ABSTRACT = {Epstein–Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) plays an important oncogenic role in 
the viral latent infection. Recently, increasing evidence indicates that the high expression of LMP1 during EBV 
lytic cycle is related to the viral lytic replication. However, the mechanism by which LMP1 regulates EBV 
lytic replication remains unclear. (−)-Epigallocatechin-3-gallate (EGCG) prevents carcinogenesis by directly 
targeting numerous membrane proteins and effectively inhibits EBV lytic cascade. Here, we demonstrated that 
LMP1 promotes EBV lytic replication through the downstream signal molecules MAPKs, including ERKs, 
p38, and JNKs. LMP1 induces the phosphorylation of p53 through MAPKs to enhance the ability of wild-type 
p53 (wt-p53) to activate expression of BZLF1 gene, while the JNKs/c-Jun signal axis appears to be involved 
in EBV lytic replication induced by LMP1 in p53 mutant manner. We provided the first evidence that EGCG 
directly targets the viral membrane LMP1 (<i>K</i><sub>d</sub> = 0.36 μM, <i>n</i> = 1) using fluorescence quenching, isothermal 
titration calorimetry (ITC) assay, and CNBR-activated Sepharose 4B pull-down affinity chromatography. 
Furthermore, we revealed that EGCG inhibits EBV lytic replication via suppressing LMP1 and thus blocking 
the downstream MAPKs/wt-p53 signal axis in AGS-EBV cells and JNKs/c-Jun signal axis in p53 mutant B95.8 
cells. Our study, for the first time, reports the binding and inhibitory efficacy of EGCG to the LMP1, which is 
a key oncoprotein encoded by EBV. These findings suggest the novel function of LMP1 in the regulation of 
EBV lytic cycle and reveal the new role of EGCG in EBV-associated malignancies through suppressing viral 
reactivation.},
DOI = {10.3727/096504021X16135618512563}
}