c-Myc and Max transregulate the mouse ornithine decarboxylase promoter through interaction with two downstream CACGTG motifs.
Ornithine decarboxylase (ODC), the first enzyme in the biosynthesis of polyamines, is essential for the process of cellular proliferation. ODC is a typical delayed early gene, as its mitogenic activation requires ongoing protein synthesis in the stimulated cells. This study provides evidence that the immediate early c-Myc protein is a potential transactivator of the ODC gene. We demonstrate that overexpression of c-Myc results in efficient activation of the ODC promoter, whereas overexpression of Max exerts a repressive effect. Both effects depend on the presence of two evolutionary conserved CACGTG motifs found in the first intron of the ODC gene. Transactivation of the ODC promoter also requires the dimerization of c-Myc with Max. Interestingly, over-expression of USF, a member of the same family of proteins which efficiently binds these two CACGTG motifs, fails to transregulate the ODC promoter. Our data suggest that c-Myc and Max are potential transcriptional regulators of the ODC promoter.
D000818:Animals; D001483:Base Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D005075:Biological Evolution; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D015870:Gene Expression; D015971:Gene Expression Regulation, Enzymologic; D007438:Introns; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009955:Ornithine Decarboxylase / Q000096:biosynthesis* / Q000235:genetics*; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D015183:Restriction Mapping; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C067850:Myc associated factor X; D016271:Proto-Oncogene Proteins c-myc; D011994:Recombinant Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C068422:Max protein, mouse; D009955:Ornithine Decarboxylase