Epstein-Barr virus-encoded EBNA-5 forms trimolecular protein complexes with MDM2 and p53 and inhibits the transactivating function of p53.
In: International Journal of Cancer, Jg. 128 (2011-02-15), Heft 4, S. 817-825
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Zugriff:
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. [ABSTRACT FROM AUTHOR]
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Titel: |
Epstein-Barr virus-encoded EBNA-5 forms trimolecular protein complexes with MDM2 and p53 and inhibits the transactivating function of p53.
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Autor/in / Beteiligte Person: | Kashuba, Elena ; Yurchenko, Mariya ; Yenamandra, Surya Pavan ; Snopok, Boris ; Szekely, Laszlo ; Bercovich, Beatrice ; Ciechanover, Aaron ; Klein, George |
Link: | |
Zeitschrift: | International Journal of Cancer, Jg. 128 (2011-02-15), Heft 4, S. 817-825 |
Veröffentlichung: | 2011 |
Medientyp: | academicJournal |
ISSN: | 0020-7136 (print) |
DOI: | 10.1002/ijc.25414 |
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