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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

Item Type:Article
Title: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
Creators Name:Batsche, E. and Lipp, M. and Cremisi, C.
Abstract: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.
Keywords:Binding Sites, Carrier Proteins, Cell Cycle Proteins, Cultured Cells, DNA-Binding Proteins, E2F Transcription Factors, Gene Expression Regulation, Genetic Promoter Regions, MYC Genes, Polyomavirus Transforming Antigens, Retinoblastoma Protein, Retinoblastoma-Binding Protein 1, Simian Virus 40, Transcription Factor DP1, Transcriptional Activation, Animals, Mice
Source:Oncogene
ISSN:0950-9232
Publisher:Nature Publishing Group (U.K.)
Volume:9
Number:8
Page Range:2235-2243
Date:August 1994
PubMed:View item in PubMed

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