Myb binding sites within the N-ras promoter repress transcription
Autor: | Brigitte Ganter, Joseph S. Lipsick |
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Rok vydání: | 1997 |
Předmět: |
Cancer Research
animal structures Protein Conformation Molecular Sequence Data Response element Repressor Biology Transfection Proto-Oncogene Proteins c-myb Transcription (biology) Proto-Oncogene Proteins Genetics Animals MYB Binding site Promoter Regions Genetic Molecular Biology Transcription factor Cells Cultured Binding Sites Base Sequence fungi Promoter Molecular biology Repressor Proteins Genes ras Trans-Activators Chickens |
Zdroj: | Oncogene. 15:193-202 |
ISSN: | 1476-5594 0950-9232 |
DOI: | 10.1038/sj.onc.1201173 |
Popis: | In vitro and in vivo methods were combined to determine the function of the three Myb binding sites (NrasI, NrasII and NrasIII) within the promoter region of the mouse N-ras gene. We found that the c-Myb DNA-binding domain can bind with high affinity to NrasI and NrasII, but with a reduced affinity to NrasIII. In contrast, the full length v-Myb protein from BM2 cells only bound to the middle one of the three sites, NrasII. Both c-Myb and v-Myb functioned as repressors and reduce the basal activity of the N-ras promoter by 60%, as determined by transient transfection experiments using different regions of the N-ras promoter. This repression required a functional Myb DNA-binding domain and could not be overcome by fusion to the potent VP16 activation domain. In electrophoretic mobility shift assays, the v-Myb protein is shown to be present in different conformations depending on its binding to the NrasII or the mim-1A site. The v-Myb conformation is thus suggested to play a critical role in the regulation of v-Myb activity. |
Databáze: | OpenAIRE |
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