THE ORNITHINE DECARBOXYLASE GENE IS A TRANSCRIPTIONAL TARGET OF C-MYC

Constitutive c-myc expression suppresses cell cycle arrest, promotes e ntry into S phase, and results in the growth factor-independent expres sion of ornithine decarboxylase (ODC; EC 4.1.1.17). The ODC gene conta ins a conserved repeat of the Myc binding site, CACGTG, in intron 1. I n this report, we demonstrate that c-Myc is a potent transactivator of ODC promoter-reporter gene constructs in fibroblasts that requires th e CACGTG repeat. These sites conferred Myc responsiveness on heterolog ous promoter constructs, suggesting that ODC is regulated by Myc at th e level of transcription initiation. Analysis of deletion and point mu tants of c-myc revealed that domains required for transactivation of t he 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.