A novel transcriptional suppressor located within a downstream intron of the BCR gene
| Autor: | M J, Stewart, G, Cox, A, Reifel-Miller, S Y, Kim, C A, Westbrook, D S, Leibowitz |
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| Rok vydání: | 1994 |
| Předmět: |
Base Composition
Binding Sites Base Sequence Transcription Genetic Molecular Sequence Data Fusion Proteins bcr-abl DNA Protein-Tyrosine Kinases Regulatory Sequences Nucleic Acid Introns Cell Line Gene Expression Regulation Proto-Oncogene Proteins Mutation Proto-Oncogene Proteins c-bcr Humans Promoter Regions Genetic HeLa Cells |
| Zdroj: | The Journal of biological chemistry. 269(14) |
| ISSN: | 0021-9258 |
| Popis: | A reciprocal translocation between chromosomes 9 and 22 creates the Philadelphia (Ph1) chromosome in chronic myelogenous leukemia. This translocation results in the fusion of the ABL and the BCR genes to form a BCR/ABL fusion gene, the product of which has a greatly increased protein tyrosine kinase activity in comparison with the normal ABL protein. The chromosome 22 translocation breakpoints are concentrated within a 5.8-kilobase region named the major break-point cluster region (Mbcr). Gel mobility shift and DNase I footprinting assays have defined binding sites for three proteins, BIF 1-3 (BCR intron factors 1-3), lying within a 427-base pair fragment of the Mbcr. This 427-base pair fragment functions as a transcriptional silencer with both the BCR as well as a heterologous promoter. The silencing is position- and orientation-independent. The transcriptional effects are greatest in chronic myelogenous leukemia cells, decreased in HeLa and B-cells, and absent in T-lymphocytes. Gel mobility shift assays show a corresponding difference in pattern when the T-lymphocyte nuclear extract is compared with other cell lines. The Mbcr appears to contain a novel group of transcriptional silencers that share a common binding motif with a recently described suppressor in the mouse Adh-1 gene. |
| Databáze: | OpenAIRE |
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