The ornithine decarboxylase gene is a transcriptional target of c-Myc.
Constitutive c-myc expression suppresses cell cycle arrest, promotes entry into S phase, and results in the growth factor-independent expression of ornithine decarboxylase (ODC; EC 4.1.1.17). The ODC gene contains a conserved repeat of the Myc binding site, CACGTG, in intron 1. In this report, we demonstrate that c-Myc is a potent transactivator of ODC promoter-reporter gene constructs in fibroblasts that requires the CACGTG repeat. These sites conferred Myc responsiveness on heterologous promoter constructs, suggesting that ODC is regulated by Myc at the level of transcription initiation. Analysis of deletion and point mutants of c-myc revealed that domains required for transactivation of the ODC promoter did not include the leucine zipper of the Myc protein. This suggests that Myc may interact with transcription factors other than Max to transactivate the ODC gene.
Bello-Fernandez
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C
Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN 38105.
Packham
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Cleveland
J L
JL
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D002999:Clone Cells; D017124:Conserved Sequence; D015971:Gene Expression Regulation, Enzymologic; D016259:Genes, myc; D006801:Humans; D007438:Introns; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009838:Oligodeoxyribonucleotides; D009955:Ornithine Decarboxylase / Q000096:biosynthesis* / Q000235:genetics; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping; D017384:Sequence Deletion; D014158:Transcription, Genetic; D014162:Transfection
D009838:Oligodeoxyribonucleotides; D016271:Proto-Oncogene Proteins c-myc; D011993:Recombinant Fusion Proteins; D015500:Chloramphenicol O-Acetyltransferase; D009955:Ornithine Decarboxylase