FIG.8.

Myc antagonizes Mnt to regulate cell fate. (A) (Left) Conventional models of transcriptional regulation by the Max network. In these models, Mad and Mnt work as antagonists of Myc. (Right) Alternatively, the Myc-Max complex can activate promoters by direct binding to E-boxes not previously occupied by other complexes. (B) In the revised model, Myc functions as an antagonist of Mnt, since Mnt loss triggers most of the“Myc” response, including Myc's transcription targets (e.g., Odc), apoptosis, accelerated proliferation, and transformation. (Right) In this scenario Myc may operate in two steps to induce its targets. First, it may displace Mnt-Max complexes from response elements, thus relieving repression. Second, when bound the Myc-Max complex may transactivate the gene. (Left) The fact that Mnt loss can activate some “Myc” transcription targets even in cells lacking all forms of Myc indicates that Myc binding may not be required to activate some of its targets, which instead are controlled through active repression.