Activation of c-myc expression by c-Abl is independent of both the DNA binding function of c-Abl and the c-myc EP site

We have shown by transient transfection assays that c-Abl increases expression of a c-myc promoter construct although to a lesser extent than v-Abl. c-Abl has been reported to bind to a specific DNA sequence, the EP element, in the hepatitis B virus enhancer. A similar sequence exists in the promote...

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Bibliographic Details
Published in:The Journal of biological chemistry 1994-08, Vol.269 (34), p.21919-21924
Main Authors: Arcinas, M, Sizer, K C, Boxer, L M
Format: Article
Language:English
Subjects:
Base Sequence
Cells, Cultured
Cross-Linking Reagents
DNA Mutational Analysis
Gene Expression Regulation - genetics
Genes, myc - genetics
hepatitis B virus
Molecular Sequence Data
Nuclear Proteins - metabolism
Promoter Regions, Genetic - genetics
Protein Binding
Proto-Oncogene Proteins c-abl - metabolism
Proto-Oncogene Proteins c-myc - biosynthesis
Proto-Oncogene Proteins c-myc - genetics
Sequence Deletion
Structure-Activity Relationship
Transcription, Genetic
Ultraviolet Rays
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Summary:We have shown by transient transfection assays that c-Abl increases expression of a c-myc promoter construct although to a lesser extent than v-Abl. c-Abl has been reported to bind to a specific DNA sequence, the EP element, in the hepatitis B virus enhancer. A similar sequence exists in the promoter region of the c-myc gene, and we have identified a potential protein binding site in this region by in vivo footprinting. Gel shift analysis demonstrated that the hepatitis B virus enhancer and c-myc sites yield identical complexes. To determine whether c-Abl activates c-myc transcription by binding directly to the promoter region, several experiments were performed. Mutation of the EP site in the c-myc promoter had no effect on transcriptional activation of c-myc by c-Abl. Next, we demonstrated that the DNA binding domain of c-Abl was not required for the transcriptional activation of c-myc. Finally, by Western blot analysis, we have determined that c-Abl is not present in the gel shift complexes formed by either the hepatitis B virus enhancer or c-myc promoter. We conclude that c-Abl activates c-myc transcription indirectly with no requirement for DNA binding by c-Abl. We also find no evidence for the interaction of c-Abl with the EP sequence of either the hepatitis B virus enhancer or the c-myc promoter.
ISSN:0021-9258
1083-351X
DOI:10.1016/S0021-9258(17)31890-2