c-Myc trans-activates the p53 promoter through a required downstream CACGTG motif.
c-Myc and wild-type p53 have been shown to play important roles in the regulation of cellular proliferation and oncogenic transformation. We have previously shown that the p53 promoter contains a conserved consensus recognition sequence for the basic-helix-loop-helix-containing proteins, identical to the specific binding site for c-Myc/Max heterodimers. Here, we demonstrate that this element, which is required for full promoter activity, is bound by in vitro translated c-Myc/Max heterodimers. Furthermore, we found that in cotransfection assays, c-Myc trans-activates the p53 promoter as well as a hybrid herpes simplex virus-thymidine kinase promoter containing multiple copies of a synthetic p53-derived c-Myc binding site. The p53 promoter deleted of the basic-helix-loop-helix consensus recognition sequence is not trans-activated by c-Myc, thus suggesting that c-Myc trans-activates the p53 promoter through the basic-helix-loop-helix recognition motif. These findings raise the possibility that the p53 gene may be a potential target for trans-activation by c-Myc in vivo.
Department of Biological Sciences, University of South Carolina, Columbia 29208.
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D
Reisman
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Elkind
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B
Roy
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Beamon
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V
Rotter
D000818:Animals; D001483:Base Sequence; D001704:Biopolymers; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D016147:Genes, Tumor Suppressor; D016259:Genes, myc; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D001704:Biopolymers; D004268:DNA-Binding Proteins; D012333:RNA, Messenger