The Epstein-Barr virus BRLF1 gene product transactivates the murine and human c-myc promoters.
A common feature of the Epstein-Barr virus (EBV)-associated malignancy, Burkitt's lymphoma, is chromosomal translocation affecting the c-myc oncogene. We report here that an EBV immediate-early (IE) protein, BRLF1 (R), transactivates the murine and human c-myc promoters. The R transactivator enhances expression from transiently transfected murine and human c-myc promoters as determined both at the CAT reporter and at the mRNA level. Transactivation of the human c-myc promoter by R occurs in several different cell lines, and this effect is reporter-gene independent. Both the P1 and P2 c-myc promoters can be activated by the EBV R IE protein, although the R-induced transactivation of P1 is greater than P2. The portion of the human c-myc promoter from -228 to -63 (relative to the P1 mRNA start site) is necessary, but not sufficient, for transactivation by R in the Louckes B-cell line. Binding of the R protein directly to the c-myc promoter could not be demonstrated, suggesting that the effect of R on c-myc activity occurs by an indirect mechanism. The ability of an EBV protein to activate c-myc expression is likely to facilitate productive viral infection and is also potentially relevant in the genesis of EBV-associated lymphomas.
Gutsch
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Biochemistry Department, State University of New York, Stony Brook 11794-5215.
Marcu
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Kenney
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D000818:Animals; D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000235:genetics; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000032:analysis / Q000096:biosynthesis; D017931:DNA Primers; D016259:Genes, myc; D004854:Herpesvirus 4, Human / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D015183:Restriction Mapping; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured; D014764:Viral Proteins
C068382:BRLF1 protein, Human herpesvirus 4; D017931:DNA Primers; D017874:Immediate-Early Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D014764:Viral Proteins; D015500:Chloramphenicol O-Acetyltransferase