title: EBNA3C regulates p53 through induction of Aurora kinase B.
abstract: 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.
authors.affiliation: 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.
authors.forename: Hem C
authors.initials: HC
authors.lastname: Jha
authors.affiliation: 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.
authors.forename: Karren
authors.initials: K
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Darine W
authors.initials: DW
authors.lastname: El-Naccache
authors.affiliation: 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.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Sun
authors.affiliation: 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.
authors.forename: Erle S
authors.initials: ES
authors.lastname: Robertson
mesh_terms: D000956:Antigens, Viral; D064107:Aurora Kinase B / Q000096:biosynthesis* / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation / Q000502:physiology; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D004790:Enzyme Induction; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics / Q000378:metabolism*; D055786:Gene Knockout Techniques; D057809:HEK293 Cells; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000821:virology; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D010766:Phosphorylation; D014162:Transfection; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics; D014764:Viral Proteins
chemical_list: D000956:Antigens, Viral; D004268:DNA-Binding Proteins; C498774:EBNA-3C, epstein-barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; D009687:Nuclear Proteins; C495901:TP53 protein, human; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D014764:Viral Proteins; C411725:lymphocryptovirus nuclear antigen 3C; C576921:AURKB protein, human; D064107:Aurora Kinase B
keywords: Aurora kinase B; EBV; oncogenesis; p53; phosphorylation