Epstein-Barr virus-encoded EBNA-5 forms trimolecular protein complexes with MDM2 and p53 and inhibits the transactivating function of p53
✍ Scribed by Elena Kashuba; Mariya Yurchenko; Surya Pavan Yenamandra; Boris Snopok; Laszlo Szekely; Beatrice Bercovich; Aaron Ciechanover; George Klein
- Book ID
- 102865205
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- French
- Weight
- 763 KB
- Volume
- 128
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Abstract
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.