Transcriptional repression and activation in the same cell type of the human c-MYC promoter by the retinoblastoma gene protein: antagonisation of both effects by SV40 T antigen.
The c-myc promoter was investigated as a possible cellular target for SV40 large T (LT) antigen. In fibroblast and epithelial cell lines, the human c-myc promoter was transactivated by LT. This transactivation was dependent of the interaction of LT with the retinoblastoma (RB) protein. The use of deletions and point mutations of the c-myc promoter demonstrated that in both cell types, the E2F binding sites are necessary for such transactivation. Unexpectedly however, over-expression of RB caused an overall transcriptional activation of the c-myc promoter. We resolved this apparent paradox by demonstrating that this activation is a combination of two antagonistic effects: transcriptional repression mediated by the E2F factor, and transcriptional activation independent of this factor. RB was also found to prevent LT-mediated transactivation, and LT inhibited RB-mediated activation independently of the E2F factor. LT therefore antagonizes both the transcriptional repression and activation mediated by RB.
Unité de Technologie Cellulaire, Institut Pasteur, Paris, France.
E
E
Batsché
M
M
Lipp
C
C
Cremisi
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000502:physiology*; D001665:Binding Sites; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D005786:Gene Expression Regulation; D016259:Genes, myc; D006801:Humans; D051379:Mice; D011401:Promoter Regions, Genetic; D016160:Retinoblastoma Protein / Q000502:physiology*; D056465:Retinoblastoma-Binding Protein 1; D013539:Simian virus 40 / Q000235:genetics*; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000502:physiology; D015533:Transcriptional Activation
D000952:Antigens, Polyomavirus Transforming; C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D016160:Retinoblastoma Protein; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors