Research Papers:

EBNA3C regulates p53 through induction of Aurora kinase B

Hem C. Jha, Karren Yang, Darine W. El-Naccache, Zhiguo Sun and Erle S. Robertson _

PDF  |  HTML  |  How to cite

Oncotarget. 2015; 6:5788-5803. https://doi.org/10.18632/oncotarget.3310

Metrics: PDF 2363 views  |   HTML 2867 views  |   ?  


Hem C. Jha1, Karren Yang1, Darine W. El-Naccache1, Zhiguo Sun1 and Erle S. Robertson1

1 Department of Microbiology and the Tumor Virology Program, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States of America


Erle S. Robertson, email:

Keywords: EBV, Aurora Kinase B, p53, Phosphorylation, oncogenesis

Received: December 21, 2014 Accepted: January 02, 2015 Published: January 21, 2015


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.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 3310