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Epstein-Barr virus-encoded EBNA-5 forms trimolecular protein complexes with MDM2 and p53 and inhibits the transactivating function of p53
- Source :
- International journal of cancer. 128(4)
- Publication Year :
- 2010
-
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.
- Subjects :
- Cancer Research
Chromatin Immunoprecipitation
Tumor suppressor gene
Immunoprecipitation
Blotting, Western
Breast Neoplasms
Plasma protein binding
Biology
hemic and lymphatic diseases
Tumor Suppressor Protein p14ARF
Monoubiquitination
Humans
RNA, Messenger
Cells, Cultured
B-Lymphocytes
Reverse Transcriptase Polymerase Chain Reaction
Lymphoblast
Ubiquitination
Proto-Oncogene Proteins c-mdm2
Surface Plasmon Resonance
In vitro
Cell biology
Oncology
Epstein-Barr Virus Nuclear Antigens
biology.protein
Cancer research
Trans-Activators
Mdm2
Female
Tumor Suppressor Protein p53
Chromatin immunoprecipitation
Protein Binding
Subjects
Details
- ISSN :
- 10970215
- Volume :
- 128
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- International journal of cancer
- Accession number :
- edsair.doi.dedup.....b86a4dca41127648d712791f99733648