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The Meq oncoprotein of Marek's disease virus interacts with p53 and inhibits its transcriptional and apoptotic activities

BACKGROUND: Marek's disease virus (MDV) is an oncogenic herpesvirus, which causes malignant lymphoma in chickens. The Meq protein of MDV, which is expressed abundantly in MDV-infected cells and in Marek's disease (MD) tumor cells, functions as a transcriptional activator and has been propo...

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Autores principales: Deng, Xufang, Li, Xiangdong, Shen, Yang, Qiu, Yafeng, Shi, Zixue, Shao, Donghua, Jin, Yamei, Chen, Hongjun, Ding, Chan, Li, Li, Chen, Puyan, Ma, Zhiyong
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2999606/
https://www.ncbi.nlm.nih.gov/pubmed/21110861
http://dx.doi.org/10.1186/1743-422X-7-348
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author Deng, Xufang
Li, Xiangdong
Shen, Yang
Qiu, Yafeng
Shi, Zixue
Shao, Donghua
Jin, Yamei
Chen, Hongjun
Ding, Chan
Li, Li
Chen, Puyan
Ma, Zhiyong
author_facet Deng, Xufang
Li, Xiangdong
Shen, Yang
Qiu, Yafeng
Shi, Zixue
Shao, Donghua
Jin, Yamei
Chen, Hongjun
Ding, Chan
Li, Li
Chen, Puyan
Ma, Zhiyong
author_sort Deng, Xufang
collection PubMed
description BACKGROUND: Marek's disease virus (MDV) is an oncogenic herpesvirus, which causes malignant lymphoma in chickens. The Meq protein of MDV, which is expressed abundantly in MDV-infected cells and in Marek's disease (MD) tumor cells, functions as a transcriptional activator and has been proposed to play an important role in oncogenic transformation. Preliminary studies demonstrated that Meq is able to bind p53 in vitro, as demonstrated using a protein-binding assay. This observation prompted us to examine whether the interaction between Meq and p53 occurs in cells, and to investigate the biological significance of this interaction. RESULTS: We confirmed first that Meq interacted directly with p53 using a yeast two-hybrid assay and an immunoprecipitation assay, and we investigated the biological significance of this interaction subsequently. Exogenous expression of Meq resulted in the inhibition of p53-mediated transcriptional activity and apoptosis, as analyzed using a p53 luciferase reporter assay and a TUNEL assay. The inhibitory effect of Meq on transcriptional activity mediated by p53 was dependent on the physical interaction between these two proteins, because a Meq deletion mutant that lacked the p53-binding region lost the ability to inhibit p53-mediated transcriptional activity and apoptosis. The Meq variants L-Meq and S-Meq, but not VS-Meq and ∆Meq, which were expressed in MD tumor cells and MDV-infected cells, exerted an inhibitory effect on p53 transcriptional activity. In addition, ∆Meq was found to act as a negative regulator of Meq. CONCLUSIONS: The Meq oncoprotein interacts directly with p53 and inhibits p53-mediated transcriptional activity and apoptosis. These findings provide valuable insight into the molecular basis for the function of Meq in MDV oncogenesis.
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spelling pubmed-29996062010-12-09 The Meq oncoprotein of Marek's disease virus interacts with p53 and inhibits its transcriptional and apoptotic activities Deng, Xufang Li, Xiangdong Shen, Yang Qiu, Yafeng Shi, Zixue Shao, Donghua Jin, Yamei Chen, Hongjun Ding, Chan Li, Li Chen, Puyan Ma, Zhiyong Virol J Research BACKGROUND: Marek's disease virus (MDV) is an oncogenic herpesvirus, which causes malignant lymphoma in chickens. The Meq protein of MDV, which is expressed abundantly in MDV-infected cells and in Marek's disease (MD) tumor cells, functions as a transcriptional activator and has been proposed to play an important role in oncogenic transformation. Preliminary studies demonstrated that Meq is able to bind p53 in vitro, as demonstrated using a protein-binding assay. This observation prompted us to examine whether the interaction between Meq and p53 occurs in cells, and to investigate the biological significance of this interaction. RESULTS: We confirmed first that Meq interacted directly with p53 using a yeast two-hybrid assay and an immunoprecipitation assay, and we investigated the biological significance of this interaction subsequently. Exogenous expression of Meq resulted in the inhibition of p53-mediated transcriptional activity and apoptosis, as analyzed using a p53 luciferase reporter assay and a TUNEL assay. The inhibitory effect of Meq on transcriptional activity mediated by p53 was dependent on the physical interaction between these two proteins, because a Meq deletion mutant that lacked the p53-binding region lost the ability to inhibit p53-mediated transcriptional activity and apoptosis. The Meq variants L-Meq and S-Meq, but not VS-Meq and ∆Meq, which were expressed in MD tumor cells and MDV-infected cells, exerted an inhibitory effect on p53 transcriptional activity. In addition, ∆Meq was found to act as a negative regulator of Meq. CONCLUSIONS: The Meq oncoprotein interacts directly with p53 and inhibits p53-mediated transcriptional activity and apoptosis. These findings provide valuable insight into the molecular basis for the function of Meq in MDV oncogenesis. BioMed Central 2010-11-26 /pmc/articles/PMC2999606/ /pubmed/21110861 http://dx.doi.org/10.1186/1743-422X-7-348 Text en Copyright ©2010 Deng et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Deng, Xufang
Li, Xiangdong
Shen, Yang
Qiu, Yafeng
Shi, Zixue
Shao, Donghua
Jin, Yamei
Chen, Hongjun
Ding, Chan
Li, Li
Chen, Puyan
Ma, Zhiyong
The Meq oncoprotein of Marek's disease virus interacts with p53 and inhibits its transcriptional and apoptotic activities
title The Meq oncoprotein of Marek's disease virus interacts with p53 and inhibits its transcriptional and apoptotic activities
title_full The Meq oncoprotein of Marek's disease virus interacts with p53 and inhibits its transcriptional and apoptotic activities
title_fullStr The Meq oncoprotein of Marek's disease virus interacts with p53 and inhibits its transcriptional and apoptotic activities
title_full_unstemmed The Meq oncoprotein of Marek's disease virus interacts with p53 and inhibits its transcriptional and apoptotic activities
title_short The Meq oncoprotein of Marek's disease virus interacts with p53 and inhibits its transcriptional and apoptotic activities
title_sort meq oncoprotein of marek's disease virus interacts with p53 and inhibits its transcriptional and apoptotic activities
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2999606/
https://www.ncbi.nlm.nih.gov/pubmed/21110861
http://dx.doi.org/10.1186/1743-422X-7-348
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