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Basic Characteristics of Mutations
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Mutation Site
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I528S |
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Mutation Site Sentence
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In another assay based on EBNA1-dependent transactivation of an OriP-harboring reporter, EBNA1 S383A, I528S, or DM showed much lower activity (< ~50%, 39%, and 10%, respectively) (Figure .3A). |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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EBNA-1 |
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Standardized Encoding Gene
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EBNA-1
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Genotype/Subtype
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- |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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Cell line
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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- |
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Location
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- |
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Literature Information
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PMID
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27009860
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Title
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ERK2 phosphorylation of EBNA1 serine 383 residue is important for EBNA1-dependent transactivation
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Author
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Noh KW,Park J,Joo EH,Lee EK,Choi EY,Kang MS
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Journal
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Oncotarget
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Journal Info
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2016 May 3;7(18):25507-15
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Abstract
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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.
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Sequence Data
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-
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