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EBNA3C regulates p53 through induction of Aurora kinase B

In multicellular organisms p53 maintains genomic integrity through activation of DNA repair, and apoptosis. EBNA3C can down regulate p53 transcriptional activity. Aurora kinase (AK) B phosphorylates p53, which leads to degradation of p53. Aberrant expression of AK-B is a hallmark of numerous human c...

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Autores principales: Jha, Hem C., Yang, Karren, El-Naccache, Darine W., Sun, Zhiguo, Robertson, Erle S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4467402/
https://www.ncbi.nlm.nih.gov/pubmed/25691063
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author Jha, Hem C.
Yang, Karren
El-Naccache, Darine W.
Sun, Zhiguo
Robertson, Erle S.
author_facet Jha, Hem C.
Yang, Karren
El-Naccache, Darine W.
Sun, Zhiguo
Robertson, Erle S.
author_sort Jha, Hem C.
collection PubMed
description In multicellular organisms p53 maintains genomic integrity through activation of DNA repair, and apoptosis. EBNA3C can down regulate p53 transcriptional activity. Aurora kinase (AK) B phosphorylates p53, which leads to degradation of p53. Aberrant expression of AK-B is a hallmark of numerous human cancers. Therefore changes in the activities of p53 due to AK-B and EBNA3C expression is important for understanding EBV-mediated cell transformation. Here we show that the activities of p53 and its homolog p73 are dysregulated in EBV infected primary cells which can contribute to increased cell transformation. Further, we showed that the ETS-1 binding site is crucial for EBNA3C-mediated up-regulation of AK-B transcription. Further, we determined the Ser 215 residue of p53 is critical for functional regulation by AK-B and EBNA3C and that the kinase domain of AK-B which includes amino acid residues 106, 111 and 205 was important for p53 regulation. AK-B with a mutation at residue 207 was functionally similar to wild type AK-B in terms of its kinase activities and knockdown of AK-B led to enhanced p73 expression independent of p53. This study explores an additional mechanism by which p53 is regulated by AK-B and EBNA3C contributing to EBV-induced B-cell transformation.
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spelling pubmed-44674022015-06-22 EBNA3C regulates p53 through induction of Aurora kinase B Jha, Hem C. Yang, Karren El-Naccache, Darine W. Sun, Zhiguo Robertson, Erle S. Oncotarget Research Paper In multicellular organisms p53 maintains genomic integrity through activation of DNA repair, and apoptosis. EBNA3C can down regulate p53 transcriptional activity. Aurora kinase (AK) B phosphorylates p53, which leads to degradation of p53. Aberrant expression of AK-B is a hallmark of numerous human cancers. Therefore changes in the activities of p53 due to AK-B and EBNA3C expression is important for understanding EBV-mediated cell transformation. Here we show that the activities of p53 and its homolog p73 are dysregulated in EBV infected primary cells which can contribute to increased cell transformation. Further, we showed that the ETS-1 binding site is crucial for EBNA3C-mediated up-regulation of AK-B transcription. Further, we determined the Ser 215 residue of p53 is critical for functional regulation by AK-B and EBNA3C and that the kinase domain of AK-B which includes amino acid residues 106, 111 and 205 was important for p53 regulation. AK-B with a mutation at residue 207 was functionally similar to wild type AK-B in terms of its kinase activities and knockdown of AK-B led to enhanced p73 expression independent of p53. This study explores an additional mechanism by which p53 is regulated by AK-B and EBNA3C contributing to EBV-induced B-cell transformation. Impact Journals LLC 2015-01-21 /pmc/articles/PMC4467402/ /pubmed/25691063 Text en Copyright: © 2015 Jha 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
Jha, Hem C.
Yang, Karren
El-Naccache, Darine W.
Sun, Zhiguo
Robertson, Erle S.
EBNA3C regulates p53 through induction of Aurora kinase B
title EBNA3C regulates p53 through induction of Aurora kinase B
title_full EBNA3C regulates p53 through induction of Aurora kinase B
title_fullStr EBNA3C regulates p53 through induction of Aurora kinase B
title_full_unstemmed EBNA3C regulates p53 through induction of Aurora kinase B
title_short EBNA3C regulates p53 through induction of Aurora kinase B
title_sort ebna3c regulates p53 through induction of aurora kinase b
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4467402/
https://www.ncbi.nlm.nih.gov/pubmed/25691063
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