Epstein-Barr virus-encoded EBNA-5 forms trimolecular protein complexes with MDM2 and p53 and inhibits the transactivating function of p53.

We report that MDM2, a negative regulator of p53, can bind to EBNA-5. Using GST pull-down assay, immunoprecipitation, surface plasmon resonance and immunostaining of lymphoblastoid cells, we found that trimolecular complexes are formed between EBNA-5, MDM2 and p53, where MDM2 serves as a bridge. The EBNA-5 binding to MDM2 counteracted ...
destabilizing effect of the latter on the p53. In ubiquitination and degradation assays in vitro, EBNA-5 inhibited p53 polyubiquitination (but not monoubiquitination) in a concentration-dependent manner. This resembles the effect of p14ARF on p53. Moreover, EBNA-5 was found to inhibit the degradation of p53 in vitro. High levels of p53 expression were maintained in LCLs. The binding of EBNA-5 to MDM2 also could impair the functional activity of p53. The p53-dependent genes P21 and VDR were not induced in EBV-infected, in contrast to mitogen-activated cells. This may explain the tolerance of established LCLs to high levels of p53 without undergoing apoptosis.
Mesh Terms:
B-Lymphocytes, Blotting, Western, Breast Neoplasms, Cells, Cultured, Chromatin Immunoprecipitation, Epstein-Barr Virus Nuclear Antigens, Female, Humans, Protein Binding, Proto-Oncogene Proteins c-mdm2, RNA, Messenger, Reverse Transcriptase Polymerase Chain Reaction, Surface Plasmon Resonance, Trans-Activators, Tumor Suppressor Protein p14ARF, Tumor Suppressor Protein p53, Ubiquitination
Int. J. Cancer
Date: Feb. 15, 2011
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