Linda Boxer

Publication Details

• 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.

  Arcinas M, Sizer KC, Boxer LM. J Biol Chem. 1994; 269 (34): 21919-24

  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.

  PubMedID: 8063836