EBNA-5, an Epstein-Barr virus-encoded nuclear antigen, binds to the retinoblastoma and p53 proteins.
Epstein-Barr virus (EBV) immortalized human lymphoblastoid cell lines express six virally encoded nuclear proteins, designated EBV nuclear antigens 1-6 (EBNA-1-6). We show that the EBNA-5 protein (alternatively designated EBNA-LP) that is required for B-cell transformation can form a molecular complex with the retinoblastoma (RB) and p53 tumor suppressor proteins. Using EBNA-5 deletion mutants, we have found that a 66-amino acid-long peptide, encoded by the W repeat of the EBV genome, is sufficient for binding. Point mutations of RB and p53 that inhibit their complexing with other DNA viral oncoproteins do not affect their binding to EBNA-5. p53 competes with RB for EBNA-5 binding. Our data suggest that the mechanisms involved in EBV transformation may include impairment of RB and p53 function.
Department of Tumor Biology, Karolinska Institute, Stockholm, Sweden.
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L
Szekely
G
G
Selivanova
K P
KP
Magnusson
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G
Klein
K G
KG
Wiman
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D000956:Antigens, Viral / Q000096:biosynthesis / Q000378:metabolism*; D001665:Binding Sites; D015153:Blotting, Western; D002051:Burkitt Lymphoma; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D019309:Epstein-Barr Virus Nuclear Antigens; D005982:Glutathione Transferase / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010455:Peptides / Q000138:chemical synthesis; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism*; D017384:Sequence Deletion; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; D004268:DNA-Binding Proteins; D019309:Epstein-Barr Virus Nuclear Antigens; D010455:Peptides; D011993:Recombinant Fusion Proteins; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D005982:Glutathione Transferase