Global Proteomic Changes Induced by the Epstein-Barr Virus Oncoproteins Latent Membrane Protein 1 and 2A

ABSTRACT The Epstein-Barr virus (EBV) oncoproteins latent membrane protein 1 (LMP1) and LMP2A constitutively activate multiple signaling pathways, and both have been shown to interact with cellular ubiquitin ligases and affect cellular ubiquitination. To detect the LMP1- and LMP2A-mediated effects o...

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Autores principales:	Robert M. DeKroon, Harsha P. Gunawardena, Rachel Edwards, Nancy Raab-Traub
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/9e431d5b1da542e784d7a890fc6de67f
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spelling	oai:doaj.org-article:9e431d5b1da542e784d7a890fc6de67f2021-11-15T16:00:25ZGlobal Proteomic Changes Induced by the Epstein-Barr Virus Oncoproteins Latent Membrane Protein 1 and 2A10.1128/mBio.00959-182150-7511https://doaj.org/article/9e431d5b1da542e784d7a890fc6de67f2018-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00959-18https://doaj.org/toc/2150-7511ABSTRACT The Epstein-Barr virus (EBV) oncoproteins latent membrane protein 1 (LMP1) and LMP2A constitutively activate multiple signaling pathways, and both have been shown to interact with cellular ubiquitin ligases and affect cellular ubiquitination. To detect the LMP1- and LMP2A-mediated effects on the global cellular proteome, epithelial cell lines expressing LMP1 or LMP2A were analyzed using label-free quantitative proteomics. To identify proteins whose ubiquitination is affected by the viral proteins, the cells were cultured in the presence and absence of deubiquitinase (DUB) and proteasome inhibitors. More than 7,700 proteins were identified with high confidence and considerably more proteins showed significant differences in expression in the presence of inhibitors. Few of the differentially expressed proteins with or without inhibitors were common between LMP1 and LMP2A, confirming that the viral proteins induce unique changes in cell expression and function. However, ingenuity pathway analysis (IPA) of the data indicated that LMP1 and LMP2A modulate many of the same cellular regulatory pathways, including cell death and survival, cell movement, and actin filament dynamics. In addition, various proteasome subunits, ubiquitin-specific peptidases and conjugating enzymes, vesicle trafficking proteins, and NF-κB and mitogen-activated protein kinase signaling proteins were affected by LMP1 or LMP2A. These findings suggest that LMP1 and LMP2A may commonly target critical cell pathways through effects on distinct genes, with many cellular proteins modified by ubiquitination and/or degradation. IMPORTANCE The Epstein-Barr virus proteins latent membrane protein 1 and 2 have potent effects on cell growth and signaling. Both proteins bind to specific ubiquitin ligases and likely modulate the cellular proteome through ubiquitin-mediated effects on stability and intracellular location. In this study, a comprehensive proteomic analysis of the effects of LMP1 and LMP2A revealed that both proteins affected proteasome subunits, ubiquitin-specific conjugases and peptidases, and vesical trafficking proteins. The data suggest that the effects of these proteins on the abundance and ubiquitination of cellular proteins are in part responsible for their effects on cell growth regulation.Robert M. DeKroonHarsha P. GunawardenaRachel EdwardsNancy Raab-TraubAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 9, Iss 3 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Robert M. DeKroon Harsha P. Gunawardena Rachel Edwards Nancy Raab-Traub Global Proteomic Changes Induced by the Epstein-Barr Virus Oncoproteins Latent Membrane Protein 1 and 2A
description	ABSTRACT The Epstein-Barr virus (EBV) oncoproteins latent membrane protein 1 (LMP1) and LMP2A constitutively activate multiple signaling pathways, and both have been shown to interact with cellular ubiquitin ligases and affect cellular ubiquitination. To detect the LMP1- and LMP2A-mediated effects on the global cellular proteome, epithelial cell lines expressing LMP1 or LMP2A were analyzed using label-free quantitative proteomics. To identify proteins whose ubiquitination is affected by the viral proteins, the cells were cultured in the presence and absence of deubiquitinase (DUB) and proteasome inhibitors. More than 7,700 proteins were identified with high confidence and considerably more proteins showed significant differences in expression in the presence of inhibitors. Few of the differentially expressed proteins with or without inhibitors were common between LMP1 and LMP2A, confirming that the viral proteins induce unique changes in cell expression and function. However, ingenuity pathway analysis (IPA) of the data indicated that LMP1 and LMP2A modulate many of the same cellular regulatory pathways, including cell death and survival, cell movement, and actin filament dynamics. In addition, various proteasome subunits, ubiquitin-specific peptidases and conjugating enzymes, vesicle trafficking proteins, and NF-κB and mitogen-activated protein kinase signaling proteins were affected by LMP1 or LMP2A. These findings suggest that LMP1 and LMP2A may commonly target critical cell pathways through effects on distinct genes, with many cellular proteins modified by ubiquitination and/or degradation. IMPORTANCE The Epstein-Barr virus proteins latent membrane protein 1 and 2 have potent effects on cell growth and signaling. Both proteins bind to specific ubiquitin ligases and likely modulate the cellular proteome through ubiquitin-mediated effects on stability and intracellular location. In this study, a comprehensive proteomic analysis of the effects of LMP1 and LMP2A revealed that both proteins affected proteasome subunits, ubiquitin-specific conjugases and peptidases, and vesical trafficking proteins. The data suggest that the effects of these proteins on the abundance and ubiquitination of cellular proteins are in part responsible for their effects on cell growth regulation.
format	article
author	Robert M. DeKroon Harsha P. Gunawardena Rachel Edwards Nancy Raab-Traub
author_facet	Robert M. DeKroon Harsha P. Gunawardena Rachel Edwards Nancy Raab-Traub
author_sort	Robert M. DeKroon
title	Global Proteomic Changes Induced by the Epstein-Barr Virus Oncoproteins Latent Membrane Protein 1 and 2A
title_short	Global Proteomic Changes Induced by the Epstein-Barr Virus Oncoproteins Latent Membrane Protein 1 and 2A
title_full	Global Proteomic Changes Induced by the Epstein-Barr Virus Oncoproteins Latent Membrane Protein 1 and 2A
title_fullStr	Global Proteomic Changes Induced by the Epstein-Barr Virus Oncoproteins Latent Membrane Protein 1 and 2A
title_full_unstemmed	Global Proteomic Changes Induced by the Epstein-Barr Virus Oncoproteins Latent Membrane Protein 1 and 2A
title_sort	global proteomic changes induced by the epstein-barr virus oncoproteins latent membrane protein 1 and 2a
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/9e431d5b1da542e784d7a890fc6de67f
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Global Proteomic Changes Induced by the Epstein-Barr Virus Oncoproteins Latent Membrane Protein 1 and 2A

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