ERK2 phosphorylation of EBNA1 serine 383 residue is important for EBNA1-dependent transactivation

作者：Noh Ka Won; Park Jihyun; Joo Eun Hye; Lee Eun Kyung; Choi Eun Young; Kang Myung Soo^*

来源：Oncotarget, 2016, 7(18): 25507-25515.

DOI：10.18632/oncotarget.8177

• Epstein-Barr virus
• EBNA1
• ERK
• phosphorylation
• inhibitor

Functional inhibition of Epstein-Barr virus (EBV)-encoded nuclear antigen 1 (EBNA1) can cause the death of EBV infected cells. In this study, a bioinformatics tool predicted the existence of putative extracellular signal-regulated kinase (ERK) docking and substrate consensus sites on EBNA1, suggesting that ERK2 could bind to and phosphorylate EBNA1. In accordance, ERK2 was found to phosphorylate EBNA1 serine 383 in a reaction suppressed by H20 (a structural congener of the ERK inhibitor), U0126 (an inhibitor of MEK kinase), and mutations at substrate (S383A) or putative ERK docking sites. Wild-type (S383) and phosphomimetic (S383D) EBNA1 demonstrated comparable transactivation function, which was suppressed by H20 or U0126. In contrast, non-phosphorylated EBNA1 mutants displayed significantly impaired transactivation activity. ERK2 knock-down by siRNA, or treatment with U0126 or H20 repressed EBNA1-dependent transactivation. Collectively, these data indicate that blocking ERK2-directed phosphorylation can suppress EBNA1-transactivation function in latent EBV-infected cells, validating ERK2 as a drug target for EBV-associated disorders.

• 出版日期2016-5-3