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ERK2 phosphorylation of EBNA1 serine 383 residue is important for EBNA1-dependent transactivation
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, suggesti...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5041921/ https://www.ncbi.nlm.nih.gov/pubmed/27009860 http://dx.doi.org/10.18632/oncotarget.8177 |
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author | Noh, Ka-Won Park, Jihyun Joo, Eun Hye Lee, Eun Kyung Choi, Eun Young Kang, Myung-Soo |
author_facet | Noh, Ka-Won Park, Jihyun Joo, Eun Hye Lee, Eun Kyung Choi, Eun Young Kang, Myung-Soo |
author_sort | Noh, Ka-Won |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5041921 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-50419212016-10-10 ERK2 phosphorylation of EBNA1 serine 383 residue is important for EBNA1-dependent transactivation Noh, Ka-Won Park, Jihyun Joo, Eun Hye Lee, Eun Kyung Choi, Eun Young Kang, Myung-Soo Oncotarget Research Paper 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. Impact Journals LLC 2016-03-18 /pmc/articles/PMC5041921/ /pubmed/27009860 http://dx.doi.org/10.18632/oncotarget.8177 Text en Copyright: © 2016 Noh et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Noh, Ka-Won Park, Jihyun Joo, Eun Hye Lee, Eun Kyung Choi, Eun Young Kang, Myung-Soo ERK2 phosphorylation of EBNA1 serine 383 residue is important for EBNA1-dependent transactivation |
title | ERK2 phosphorylation of EBNA1 serine 383 residue is important for EBNA1-dependent transactivation |
title_full | ERK2 phosphorylation of EBNA1 serine 383 residue is important for EBNA1-dependent transactivation |
title_fullStr | ERK2 phosphorylation of EBNA1 serine 383 residue is important for EBNA1-dependent transactivation |
title_full_unstemmed | ERK2 phosphorylation of EBNA1 serine 383 residue is important for EBNA1-dependent transactivation |
title_short | ERK2 phosphorylation of EBNA1 serine 383 residue is important for EBNA1-dependent transactivation |
title_sort | erk2 phosphorylation of ebna1 serine 383 residue is important for ebna1-dependent transactivation |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5041921/ https://www.ncbi.nlm.nih.gov/pubmed/27009860 http://dx.doi.org/10.18632/oncotarget.8177 |
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