Epstein-Barr virus nuclear protein EBNA-3C interacts with the human metastatic suppressor Nm23-H1: a molecular link to cancer metastasis.
Epstein-Barr virus (EBV) is an oncogenic virus associated with a number of human malignancies including Burkitt lymphoma, nasopharyngeal carcinoma, lymphoproliferative disease and, though still debated, breast carcinoma. A subset of latent EBV antigens is required for mediating immortalization of primary B-lymphocytes. Here we demonstrate that the carboxy-terminal region of the essential latent antigen, EBNA-3C, interacts specifically with the human metastatic suppressor protein Nm23-H1. Moreover, EBNA-3C reverses the ability of Nm23-H1 to suppress the migration of Burkitt lymphoma cells and breast carcinoma cells. We propose that EBNA-3C contributes to EBV-associated human cancers by targeting and altering the role of the metastasis suppressor Nm23-H1.
Subramanian
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Program in Cellular and Molecular Biology, Department of Microbiology and Immunology and the Comprehensive Cancer and Geriatrics Center, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Cotter
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MA
Robertson
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D000956:Antigens, Viral / Q000378:metabolism*; D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism; D017931:DNA Primers; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*; D054778:NM23 Nucleoside Diphosphate Kinases; D009362:Neoplasm Metastasis; D009701:Nucleoside-Diphosphate Kinase; D011485:Protein Binding; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000956:Antigens, Viral; D017931:DNA Primers; D054778:NM23 Nucleoside Diphosphate Kinases; D014157:Transcription Factors; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins